Learn about brain health and nootropics to boost brain function
Boosting brain protein levels may slow decline from Alzheimer’s
A study published in the journal Brain shows that increases in protein levels with new Alzheimer’s drugs can explain the slowing of cognitive impairment at least as well as the reduction in amyloid plaques.
During a study challenging the idea that newly approved monoclonal antibodies reduce cognitive decline in Alzheimer’s patients by clearing amyloid, University of Cincinnati researchers found that the unintended increase in levels of a critical brain protein correlates equally well with cognitive benefits.
Led by UC’s Alberto Espay, MD, the research was published in the journal Brain on Sept. 11.
For decades, the prevailing theory in the field has stated that a protein made up of 42 amino acids called amyloid-beta 42 (Aβ42) hardens into clumps called amyloid plaques, and those plaques damage the brain, causing Alzheimer’s disease.
Espay and team have hypothesized that normal, soluble Aβ42 in the brain is crucial for neuron health and that the loss of Aβ42, rather than the buildup of plaques, drives Alzheimer’s. This includes published research that suggests dementia occurs not when plaque levels are high but when Aβ42 levels drop very low.
According to Espay’s research, the transformation of Aβ42 into plaques appears to be the brain’s normal response to biological, metabolic or infectious stress.
“Most of us will accrue amyloid plaques in our brains as we age, and yet very few of us with plaques go on to develop dementia,” said Espay, professor of neurology in the UC College of Medicine and director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute. “Yet the plaques remain the center of our attention in biomarker development and therapeutic strategies.”
Recently, several new monoclonal antibody medications designed to remove amyloid from the brain were approved after showing they lessened cognitive decline in clinical trials.
Espay and his colleagues noticed that these drugs unintentionally increased levels of Aβ42.
“Amyloid plaques don’t cause Alzheimer’s, but if the brain makes too much of it while defending against infections, toxins or biological changes, it can’t produce enough Aβ42, causing its levels to drop below a critical threshold,” Espay explained. “That’s when dementia symptoms emerge.”
The team analyzed data from nearly 26,000 patients enrolled in 24 randomized clinical trials of these new antibody treatments, assessing cognitive impairment and differences in levels of Aβ42 before and after treatment. They found that higher levels of Aβ42 after treatment were independently associated with slower cognitive impairment and clinical decline.
“All stories have two sides — even the one we have told ourselves about how anti-amyloid treatments work: by lowering amyloid,” Espay said. “In fact, they also raise the levels of Aβ42. Even if this is unintended, it is why there may be a benefit. Our study shows that we can predict changes in cognitive outcomes in anti-amyloid trials at least as well by the increases in Aβ42 as by the decreases in amyloid.”
Espay said these findings fit well into his larger hypothesis about the root cause of Alzheimer’s, as increasing levels of Aβ42 appear to improve cognition.
“If the problem with Alzheimer’s is the loss of the normal protein, then increasing it should be beneficial, and this study showed that it is,” he said. “The story makes sense: Increasing Aβ42 levels to within the normal range is desirable.”
However, Espay believes these results also present a conundrum for clinicians because removing amyloid from the brain is toxic and may cause the brain to shrink faster after antibody treatment.
“Do we give patients an anti-protein treatment to increase their protein levels? I think the end, increasing Aβ42, doesn’t justify the means, decreasing amyloid,” Espay said. Therapies that directly increase Aβ42 levels without targeting amyloid are a focus of research for Espay and his group.
How the brain’s inner chamber governs our state of consciousness
by University of Michigan Schematic illustration of the primary conclusion. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-51837-1 In hospital operating rooms and intensive care units, propofol is a drug of choice, widely used to sedate patients for their comfort or render them fully unconscious for invasive procedures.
Propofol works quickly and is tolerated well by most patients when administered by an anesthesiologist. But what is happening inside the brain when patients are put under and what does this reveal about consciousness itself?
Investigators at U-M who are studying the nature of consciousness have successfully used the drug to identify the intricate brain geometry behind the unconscious state, offering an unprecedented look at brain structures that have traditionally been difficult to study.
“Consciousness has been the subject of study from various perspectives and understanding the neurobiological foundations of consciousness carries major implications of multiple medical disciplines such as neurology, psychiatry and anesthesiology,” said Zirui Huang, Ph.D., Research Assistant Professor in the Department of Anesthesiology at U-M Medical School.
To date, researchers have debated about how anesthetics suppress consciousness. Specifically, whether the site of action lies primarily in the thalamus, an egg-shaped structure deep within the brain, which receives information from what we see, touch and hear, or in the cerebral cortex , which processes that information in complex ways.
A study published in the journal Nature Communications and led by Huang, George Mashour, M.D., Ph.D. and Anthony G. Hudetz, Ph.D., of the U-M Center for Consciousness Science, outlines for the first time in humans how the connections among brain cells within those two important areas are modified by propofol. The paper is titled “Propofol Disrupts the Functional Core-Matrix Architecture of the Thalamus in Humans.”
In healthy volunteers , they mapped changes in the brain’s architecture before, during and after propofol sedation, guided by functional magnetic resonance imaging (fMRI). This enabled them to monitor blood flow to areas of the brain as the study participants entered and exited an unconscious state.
At baseline, explained Huang, the thalamus has a balanced level of activity of both specific nuclei (clusters of brain cells) that send sensory information to highly defined areas of the cortex—known as unimodal processing—and nonspecific nuclei that send information more diffusely throughout a higher layer of the cortex, known as transmodal processing.
The team found that, under deep sedation, the thalamus showed a drastic reduction in activity in clusters of brain cells responsible for transmodal processing, leading to a dominant unimodal pattern—suggesting that while sensory inputs are still received, there is no integration of those inputs.
“The field has been focusing on anesthetic effects in the thalamus and cortex for more than two decades—I believe this study significantly advances the neurobiology,” said George Mashour, M.D., Ph.D., Professor of Anesthesiology and Pharmacology, and founder of the U-M Center for Consciousness Science.
Next, they discovered the specific cell types that played a role in the shift to an unconscious state and their relationship to the change in thalamic processing. The thalamus contains at least two distinct cell types, said Huang, core cells and matrix cells.
“We now have compelling evidence that the widespread connections of thalamic matrix cells with higher order cortex are critical for consciousness,” says Hudetz, Professor of Anesthesiology at U-M and current director of the Center for Consciousness Science.
Imagining that the cortex is layered like an onion, core cells connect to lower layers while matrix cells connect to higher layers in a more spread-out manner.
By measuring mRNA expression signatures—like I.D. badges for the cells—they were able to see that a disruption in the activity of matrix cells played a greater role in the transition to unconsciousness than core cells. An additional surprise was that GABA, a major inhibitory transmitter in the brain usually thought to be key to propofol’s actions, did not appear to play as prominent a role as expected.
“The results suggest that loss of consciousness during deep sedation is primarily associated with the functional disruption of matrix cells distributed throughout the thalamus,” said Huang.
More information: Huang, Z., et al. Propofol disrupts the functional core-matrix architecture of the thalamus in humans. Nature Communications (2024). DOI: 10.1038/s41467-024-51837-1
Provided by University of Michigan
Unlock Potential With Neuroscience: Easy Ways To Boost Your Brainpower
Unlock Potential With Neuroscience: Easy Ways To Boost Your Brainpowergetty Have you ever tried to implement a new idea or mindset only to feel like you’re hitting a wall? That’s because so much of what we do is shaped by deep-rooted patterns in our brains. I once interviewed John Sanei, a futurist known for making complex ideas click. Recently, he shared a compelling analogy: think of neurology as your hardware and psychology as your software . His point? You can’t expect new programs to run smoothly on outdated systems. If we want to adapt, thrive, and truly future-proof ourselves, we need to update both. Understanding Neuroscience: The Brain’s Hardware and How It Shapes Curiosity Neuroscience is the study of the nervous system —specifically, the brain—and how it affects our thoughts, emotions, and actions. Think of it as the hardware. It’s the actual structure—the neurons, synapses, and networks—that form our thinking processes. The brain isn’t static; it’s dynamic and malleable, capable of rewiring itself through a process known as neuroplasticity . This means we’re not stuck with the same patterns forever; we can change how we think and behave by reshaping our brain’s wiring. Psychology and Emotional Intelligence: The Software That Runs on This Brain Hardware John Sanei’s analogy goes deeper when we consider psychology as the software running on our neurological hardware. Psychology focuses on our thoughts, feelings, and behaviors—essentially, the operating system of the mind. It examines why we do what we do, based on our past experiences, environment, and social conditioning. If we are only updating our psychology—our ways of thinking and behaving—without considering how it’s supported by the brain’s neurological “hardware,” we may find ourselves unable to sustain meaningful change.
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I’ve explored this connection between thoughts, emotions, and behaviors in my own research. For my doctoral dissertation, I studied the impact of emotional intelligence on performance , which dives into how understanding and managing our feelings (the psychological software) can significantly influence how we act and perform. Emotional intelligence also has a neurological component—it’s deeply rooted in how our brain processes emotions and reacts to different situations. Take the curious case of Phineas Gage , for example. After a horrific accident in which an iron rod passed through his skull, damaging parts of his frontal lobes, Gage’s personality and emotional responses changed drastically. His case became a cornerstone in understanding how brain structure (hardware) impacts emotional regulation (software), illustrating just how interconnected our neurology and psychology truly are. CEO: C-suite news, analysis, and advice for top decision makers right to your inbox.
By signing up, you agree to receive this newsletter, other updates about Forbes and its affiliates’ offerings, our Terms of Service (including resolving disputes on an individual basis via arbitration), and you acknowledge our Privacy Statement . Forbes is protected by reCAPTCHA, and the Google Privacy Policy and Terms of Service apply. Why Curiosity Is Essential for Rewiring Your Brain and Upgrading Mental Hardware Curiosity isn’t just about asking more questions—it’s a neurological workout. When we’re curious, we’re actively engaging parts of the brain that promote learning and adaptability. It’s like hitting the refresh button on your brain’s hardware. Curiosity pushes us to challenge our assumptions, explore new ideas, and be more open to change. It’s not just an intellectual exercise; it’s a way to keep the brain flexible, agile, and primed for growth.
If we hang onto the way things have always been done—clinging to the familiar without questioning why—we become stuck in outdated patterns. But when we practice curiosity, we do more than just update our mental software; we make sure the brain’s hardware is ready to support new and innovative ideas. Rewiring the Brain Through Curiosity: The Neuroscience Behind It When you cultivate curiosity, you’re essentially rewiring your brain for success. Neuroplasticity means our brains are constantly forming new connections. When we engage in activities that foster curiosity—whether it’s learning a new skill, challenging a long-held belief, or simply asking “what if?” more often—we create new neural pathways that make us more adaptable and open to change. This is crucial for breaking free from status-quo thinking and driving both personal and professional growth. How Curiosity Helps Overcome Resistance to Changegetty How Curiosity Helps Overcome Resistance to Change
Here’s where John’s analogy really comes into play. You can attend all the leadership workshops or read every self-help book under the sun, but if your brain isn’t set up to embrace and implement these new ideas, you’re not going anywhere. That’s why it’s critical to understand how the brain works and use curiosity as a tool to rewire it for greater adaptability. Curiosity cuts through the noise of fear and resistance and creates space for new connections, both neurologically and psychologically. How to Make Curiosity Part of Your Daily Brain Traininggetty How to Make Curiosity Part of Your Daily Brain Training
To upgrade our brain’s “hardware” to support new, cutting-edge “software” of ideas, we need to cultivate a daily practice of curiosity. This means: Ask More Questions : Challenge your assumptions and ask “why” more often. Not just in meetings, but in everyday life.
Expose Yourself to New Experiences : Whether it’s picking up a new hobby, reading a book outside your usual genre, or simply taking a different route to work—give your brain a chance to create new connections.
Embrace Discomfort : Growth doesn’t happen in the comfort zone. Push yourself to explore ideas that make you uncomfortable or challenge your current beliefs.
The Bottom Line: Future-Proof Your Brain with Curiosity
If you want to be ready for whatever comes next, you’ve got to think beyond just changing the way you think—you need to change the way your brain is wired to think. Curiosity keeps our minds sharp, our brains adaptable, and our perspectives fresh. Commit to being curious every day, challenge what you know, […]
3 Effective ways to maintain optimal brain performance for people over 60
Tags: aging secrets , alternative medicine , anti-aging , brain health , cognitive function , cognitive health , cognitive stimulation , exercise , fitness , goodhealth , goodmedicine , goodscience , group activities , healing arts , health science , natural health , natural medicine , physical activity , social interaction , tips Research shows that staying physically active has a big impact on brain health – even for people over 60 . From sharper memory to better problem-solving skills, the advantages of regular exercise are clear.
However, many older adults don’t participate in physical activities that are tailored to their needs. Low motivation and limited access to suitable exercises are common barriers. Often, caregivers resort to repetitive, low-impact activities, like gentle stretching, walking or yoga, due to seniors’ declining cognitive and physical abilities. While these activities are helpful, there’s a growing understanding that combining various types of exercises offers greater benefits. (Related: How to keep your brain healthy and sharp as you age .)
Researchers are exploring effective ways to enhance both the cognitive and physical abilities of older adults. The most promising strategies include three main components: Engage in complex physical activities
Physical exercise is essential not just for the body but also for the brain – particularly as people age. For seniors, staying active through aerobic exercises, like cycling, swimming or walking, can lead to significant cognitive benefits. These activities improve blood flow to the brain, encourage the growth of new neurons and enhance attention and memory.
Moderate cardio workouts are especially beneficial because they improve overall cardiovascular health, which, in turn, increases oxygen flow to the brain. This enhanced oxygen supply helps generate new neurons in the hippocampus, a crucial area for memory. To maximize these benefits, exercise routines should combine cardio with balance, coordination, flexibility and strength training.
Activities that require complex motor skills and coordination are particularly effective in boosting cognitive functions , such as attention, memory and mental flexibility. Combine physical activity with cognitive stimulation
Pairing physical exercise with cognitive challenges can greatly enhance brain health. Engaging the brain during workouts, such as by planning a move or remembering a sequence of steps, helps keep cognitive skills sharp. This combination of mental and physical exercise can produce synergistic effects – improving overall cognitive function more than either type of activity alone.
The brain functions as the control center for all bodily movements, relying on cognitive abilities like adaptability, concentration, learning and reasoning. These skills help people interact with their environment and maintain a good quality of life.
Contrary to common belief, the brain does not continuously deteriorate with age. While some decline is natural after people turn 45, the brain retains its ability to adapt and form new connections – known as cerebral plasticity – throughout life. A stimulating lifestyle can help build a cognitive reserve that mitigates the effects of aging.
Activities, such as brain games and puzzles can also be effective as they help improve concentration, focus and memory and make people more alert in daily activities. Although they may not prevent cognitive decline, they can slow it down.
It is crucial to keep these games challenging and varied to avoid the mind slipping into “autopilot.” Additionally, changing up daily routines or learning new skills can further challenge the brain – keeping both the logical left side and the creative right side engaged. Participate in group activities that lead to social interaction
Social interaction is another crucial component for maintaining cognitive health in seniors. Engaging in group activities, such as going on outings, joining clubs or volunteering, can help combat loneliness and reduce the risk of anxiety and depression. Social activities also provide intellectual stimulation and opportunities for new learning experiences – contributing to better brain fitness.
Working out in groups, especially through cooperative and competitive sports, like basketball or handball, offers both cognitive and physical benefits. These sports challenge balance, cardiovascular endurance, coordination, flexibility and strength. They also create dynamic, ever-changing situations that require adaptability and quick thinking – promoting cognitive engagement and resilience.
Recent studies have shown that team sports can improve memory and planning skills in older adults – making them an excellent choice for maintaining cognitive health.
Another innovative approach is using “exergames” – video games that combine physical activity with cognitive tasks, These games, which became popular with consoles, like the Microsoft Kinect, Nintendo Wii and Switch, encourage players to move while engaging in activities that require balance, offer an even more immersive experience by combining real and virtual elements – providing high physical and cognitive stimulation. Studies suggest that these interactive games may be more effective at improving cognitive abilities than traditional exercises.
A study published in GeroScienc e explored the impact of this advanced type of exergame . The study compared an immersive wall exergame program to a traditional muscle strengthening and walking routine – finding that the exergame might offer superior cognitive benefits for seniors.
The unique features of these new-generation exergames, such as their complex motor tasks, immersive environments, intense physical demands, opportunities for social interaction and virtual cognitive challenges, make them an exciting multi-dimensional training option for older adults.
These qualities suggest that Interactive Wall Exergames could be particularly effective in enhancing both cognitive and physical health – providing a comprehensive and fun way to stay active.
By combining real-world physical movement with digital gameplay, these games challenge players to think on their feet – improving mental agility and motor skills enjoyably. This multi-domain approach to training not only keeps seniors physically fit but also mentally sharp – offering a holistic way to combat age-related cognitive decline .
Watch this video to learn more about the benefits of exergames for older people .
This video is from the Daily Videos channel on Brighteon.com . More related stories:
Exercise preserves brain cells and prevents memory loss .
Aerobic exercise improves memory and brain power in older adults .
Adding 6 minutes of intense exercise to your daily routine can help support brain health in middle age .
Sources include:
StudyFinds.org NZHerald.co.NZ TheConversation.com SeniorFitness.org […]
Anti-inflammatory diet helps with cardiovascular and metabolic diseases, cuts dementia risk by 31%
09/06/2024 // Lance D Johnson // Views
Tags: Alzheimer’s disease , anti-inflammatory diet , avocado , berries , brain function , brain health , Cardiometabolic diseases , cognitive health , dementia , food is medicine , goodfood , goodhealth , goodmedicine , goodscience , heart disease , Herbs , longevity , Mushrooms , natural cures , natural medicine , nutrients , nuts , prevention , research , seeds , stroke , systemic inflammation , Type 2 Diabetes Adhering to an anti-inflammatory diet could reduce the risk of developing dementia by 31 percent . A recent study published in JAMA Open Network found that anti-inflammatory dietary choices can influence brain health into old age, particularly for individuals with existing cardiometabolic diseases. Anti-inflammatory foods help with cardiovascular and metabolic conditions, reducing dementia risk
The current study examined over 80,000 adults aged 60 and older, utilizing data from the UK Biobank. Participants were monitored for up to 15 years, with a median follow-up period of 12.4 years. The research specifically focused on individuals with cardiometabolic diseases (CMDs), such as heart disease, Type 2 diabetes and stroke, which are known to increase dementia risk.
Individuals with CMDs who followed an anti-inflammatory diet experienced a significant 31 percent reduction in dementia risk. This suggests that dietary modifications could play a crucial role in managing dementia risk , especially for those already vulnerable due to other health conditions.
Dementia, characterized by a decline in memory and cognitive function, is often associated with damage to brain cells. Alzheimer’s disease is the most common form of dementia. Previous research has established a connection between diet and dementia risk, with certain dietary patterns potentially slowing Alzheimer’s progression. Cardiometabolic diseases are known to heighten the risk of dementia.
Inflammation can stifle blood flow to the brain, cutting off oxygen and important nutrients, thereby starving the brain. Abigail Dove, the lead author of the study, pointed out that CMDs such as Type 2 diabetes and heart disease are indicators of inflammation and both inflammatory conditions individually increase dementia risk by 1.5 to 2 times. This risk is compounded when individuals have multiple CMDs.
The study suggests that anti-inflammatory diets significantly mitigate the risk by reducing systemic inflammation within the cardiovascular system, which is common in individuals with CMDs. Dove explains that inflammation can accelerate brain cell damage, leading to cognitive decline. For instance, CMDs like diabetes and heart disease can disrupt blood flow to the brain and damage brain cells, contributing to the development of dementia. Dove said that Type 2 diabetes exhausts the normal functions of the brain. “When excess sugar from the blood enters the brain, it can break down the protective coating that surrounds brain cells, making them less efficient and more vulnerable to damage,” Dove said, “Stroke occurs when blood supply to a part of the brain is cut off, essentially suffocating brain cells and leaving severely damaged tissue behind.” Anti-inflammatory foods should form the basis of government dietary guidelines
For individuals interested in adopting an anti-inflammatory diet , Dove and other experts recommend including foods such as berries, nuts, fatty fish, avocados, green tea, olive oil, vegetables, turmeric and mushrooms. Conversely, reducing intake of sugar, refined carbohydrates, fried foods and alcohol may also help manage inflammation.
In the study, researchers assessed participants’ diets using a detailed questionnaire, analyzing 206 foods and 32 drinks. Instead of focusing solely on specific foods, the study evaluated the inflammatory impact of nutrients and used this data to calculate an overall inflammation score for each diet.
Participants were divided into three groups based on their diet’s inflammatory impact: anti-inflammatory, pro-inflammatory and neutral. MRI scans were used to measure brain volume, revealing that lower systemic inflammation was associated with healthier brain markers and reduced dementia risk. The inflammatory diet was associated with neurodegeneration, loss of volume in the hippocampus region of the brain, which is responsible for memory processing.
Anti-inflammatory foods like fish, nuts, roots vegetables, berries, herbs and mushrooms improved cardiometabolic diseases; whereas, sugary foods, fried foods and refined carbohydrates worsened these health conditions. Studies like these can help pave the way for new dietary guidelines. The USDA food pyramid desperately needs an overhaul. Instead of including 12 servings of bread, cereal and pasta, it should include things like spirulina , beet root, turmeric, hawthorn berry , pomegranate, blueberries, lion’s mane mushroom , cinnamon and many other nutrient-dense foods. Anti-inflammatory foods should provide the basis of any diet, for longevity and healthy cardiovascular and brain function into old age.
Sources include:
TheEpochTimes.com
JAMANetwork.com
Frontiersin.org
Naturalpedia.com
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Alzheimer’s Breakthrough: New Drug Shows Promise in Reversing Memory Loss and Cognitive Decline
Researchers at Auburn University have found that the drug troriluzole can intervene early in Alzheimer’s disease progression in mice, maintaining normal brain function and improving memory, signaling hope for effective treatment strategies. New research reveals a potential breakthrough in Alzheimer’s treatment, showing that the drug troriluzole can reverse memory loss and cognitive decline in mice.
The study found that troriluzole reduced harmful glutamate levels and improved cognitive functions, suggesting its potential to maintain healthy brain function and possibly slow the disease’s progression. Novel Drug Rescues Memory Loss in Alzheimer’s Mouse Model
In a recent breakthrough in Alzheimer’s disease research, Auburn University scientists have studied a new drug, troriluzole, that can prevent brain changes leading to memory loss and cognitive decline in a mouse model of the disease. This study, recently published in the Journal of Neurochemistry , is the first to show how troriluzole can target early-stage alterations associated with Alzheimer’s, providing new hope for potential treatments.
Dr. Miranda Reed, a Professor in the department of Drug Discovery at Auburn University and Delivery and the studies main researcher, noted that “by examining how drug treatments can intervene early in the disease process, we aim to develop therapies that might prevent or even cure Alzheimer’s.”
“This study also highlights how scientific advancements can transform our understanding of complex diseases like Alzheimer’s,” said Dr. Michael Gramlich, an Assistant Professor of Biophysics and the study’s other main researcher. Shown are representative heatmap visualization of spatial occupancy during probe trials of the Morris water maze. The warmer the colors correlate with an increased time spent in that area. Credit: Dr. Michael Gramlich & Dr. Miranda Reed Groundbreaking Effects on Alzheimer’s Disease
Alzheimer’s disease affects millions of people worldwide, causing progressive memory loss, confusion, and eventually the inability to perform basic tasks. Despite decades of research, a cure remains elusive. Alzheimer’s is characterized by the accumulation of amyloid plaques and tau tangles in the brain, which disrupt neural communication. In the early stages, excessive levels of the neurotransmitter glutamate cause damaging overactivity in synapses, the connections between nerve cells.
The study conducted by Auburn University researchers, led by Drs. Miranda Reed and Michael Gramlich, investigated how troriluzole, a novel drug, can maintain normal brain function in mice genetically modified to replicate early Alzheimer’s stages. The results are compelling: troriluzole not only reduced harmful glutamate levels but also improved memory and learning in the mice, suggesting a maintenance of healthy brain function.
“Our research demonstrates that by targeting synaptic activity early, we may be able to prevent or slow the progression of Alzheimer’s. This could revolutionize the way we approach treatment for this disease,” noted both researchers.
How Troriluzole Works
In the Auburn study, mice treated with troriluzole showed a significant reduction in synaptic glutamate levels and decreased brain hyperactivity. These molecular changes led to tangible improvements: the treated mice performed better in memory tests, such as navigating mazes, indicating that their cognitive functions were restored.
“These findings are promising because they suggest that troriluzole can protect the brain at a fundamental level, starting with molecular changes and resulting in improved cognitive abilities,” said Dr. Reed. “It’s like repairing an engine before it fails completely.”
Impact of Collaborative Research
This research was a collaborative effort involving Auburn University’s College of Science and Mathematics, the Harrison College of Pharmacy, and the Center for Neuroscience Initiative, along with private researchers and students. The team’s combined expertise in neuroscience and pharmacology was crucial to the study’s success.
“This collaboration blends basic science and pharmaceutical research to tackle one of the most challenging neurological issues of our time,” Dr. Gramlich emphasized. “Our work not only enhances scientific understanding of Alzheimer’s disease but also offers a potential new treatment that could improve the lives of millions worldwide.”
Looking Forward
While the results in mice are encouraging, the researchers emphasize the need for further studies to determine how troriluzole works at different stages of disease progression.
Reference: “Troriluzole rescues glutamatergic deficits, amyloid and tau pathology, and synaptic and memory impairments in 3xTg-AD mice” by Jeremiah Pfitzer, Priyanka D. Pinky, Savannah Perman, Emma Redmon, Luca Cmelak, Vishnu Suppiramaniam, Vladimir Coric, Irfan A. Qureshi, Michael W. Gramlich and Miranda N. Reed, 30 August 2024, Journal of Neurochemistry .
DOI: 10.1111/jnc.16215
New Research Reveals What Ozempic Does to Your Brain: It May Reduce the Risk of Dementia 48 percent
Odds are you’ve heard of GLP-1 drugs like Ozempic for managing type 2 diabetes and shedding pounds. But have you ever wondered what Ozempic does to your brain? Recent research suggests it might do far more than regulate blood sugar. It could also play a role in reducing the risk of dementia.We asked the experts to weigh in on the latest research and clinical trials. GLP-1 drugs do more than manage glucose and aid weight loss
Medications known as GLP-1 agonists are FDA-approved for diabetes management and some for weight loss. GLP-1 agonists mimic a natural hormone to regulate insulin production, digestion and appetite.
But the drug used to manage diabetes is now potentially offering unexpected benefits. Semaglutide — the active ingredient in Ozempic and Wegovy — shows promise in reducing the risk of cardiovascular and kidney diseases , fatty liver disease and even obesity-related cancers . What Ozempic does to your brain
Any brain-related benefits remain speculative at this stage, explains Gregory Barone, DO , an endocrinologist with New Jersey-based Cooper University Health Care. “The outcome-based data is really promising for this drug class,” Dr. Barone says. “But a lot is still up for the scientists of the world to sort out.”
Emerging studies suggest the diabetes drug might protect against the risk of cognitive decline, including dementia, Parkinson’s and Alzheimer’s. It could also curb addictive behaviors, such as problems with nicotine dependence. However, the exact mechanisms behind these effects are still unclear.
“The question is, ‘why?’” Dr. Barone says. “Is it something inherent about the semaglutide molecule itself, or are these benefits due to secondary effects like weight loss, decreased inflammation, or changes in consumption habits?” Ozempic may reduce the risk of dementia 48 percent
Carolina Rudah/Getty The idea that diabetes medication could protect against cognitive decline might seem surprising, but the evidence is growing. A recent University of Oxford study, published in Lancet eClinicalMedicine , suggests that GLP-1 agonists like Ozempic may lower the risk of developing dementia in patients with diabetes by 48 percent compared to those taking sitagliptin (Januvia).
Patients prescribed semaglutide had a reduced risk of developing 22 brain and psychiatric disorders within one year of treatment compared to those on other diabetes drugs . Since diabetes is a known risk factor for cognitive decline, this makes GLP-1 medications like Ozempic especially promising, says Dr. Barone.
However, important questions remain, including how GLP-1 agonists like Ozempic protect the brain and to what extent. The Oxford study was observational, meaning it shows associations but doesn’t prove cause and effect, Dr. Barone notes.
“Dementia can develop through various pathways, one of the more common being vascular dementia, which is related to blood vessel health,” Dr. Barone says. “Since these medications improve cardiovascular outcomes — like reducing the risk of heart disease and stroke — it’s not a big leap to think they might also help maintain vascular health in the brain, potentially reducing the risk of vascular dementia.”
“But dementia progresses at different rates in different people, so it’s challenging to say if a patient’s trajectory has changed,” he adds. More ways Ozempic affects your brain
While the focus of recent studies has been on the risk of cognitive problems, researchers are also exploring Ozempic’s potential in treating other brain-related conditions, including addictions like gambling and alcohol dependence.
The University of Oxford study also found that Ozempic significantly reduced nicotine dependence in patients, suggesting it may play a role in reducing addictive behaviors. GLP-1 drugs like Ozempic act on cravings in the brain
fcafotodigital GLP-1 agonists reduce constant thoughts about hunger. This allows patients to think more clearly and stay focused, says Dr. Barone. The reduction in food preoccupation could extend to other cravings as well.
“People who struggle with obesity often have abnormal brain signaling, where food is perceived as an addiction — similar to how smokers or alcoholics crave or depend on their fixes,” says Dr. Barone.
“We know semaglutide works primarily at the appetite center, but it’s suspected that the nearby reward center could also be involved,” he notes. “There may be some cross-signaling that blunts cravings not just for food, but for other addictive behaviors.” What Ozempic does to your brain: The bottom line
While the science behind these additional Ozempic benefits is plausible, Dr. Barone says it’s far too early to say if and how GLP-1 drugs can be repurposed to protect the brain.
“The outcome-based data we have is incredibly promising, particularly for diabetes, heart disease and kidney health ,” Dr. Barone adds. “As for cognitive benefits, we’re still waiting for more concrete evidence.”
Fore more on semaglutide and GLP-1 drugs like Ozempic:
What Happens When You Stop Taking Ozempic? How to Stop Medication Safely
New Research Reveals GLP-1 Weight Loss Drugs May Help People Quit Smoking
Ozempic Can Be a Sneaky Cause of Hair Loss — Dermatologists Reveal How to Restore Volume
This content is not a substitute for professional medical advice or diagnosis. Always consult your physician before pursuing any treatment plan .
Matcha green tea may improve sleep, social functioning in older adults
Can matcha tea help improve brain health as we age? A new study investigates. Image credit: Martí Sans/Stocksy. Japanese researchers recently evaluated the potential cognitive benefits of matcha green tea (powdered green tea) for older adults.
Green teas contain antioxidants that can provide health benefits and even prevent some diseases.
The researchers who conducted the current study wanted to see whether this range of benefits can extend to cognitive benefits.
While the scientists learned that matcha green tea may help with social cognition and sleep, they did not find a connection between matcha and other cognitive improvements.
Millions of people in the United States live with dementia, and according to the Alzheimer’s Association , this number is only set to grow unless researchers make significant advances in the diagnosis and treatment of this memory-affecting condition.
As dementia cases continue to climb, scientists continue to research ways people can improve their cognitive health.
Researchers in Japan recently turned to matcha green tea to find out whether its properties can provide cognitive benefits.
The study did not quite yield the results the researchers expected since participants who took matcha did not make improvements in memory and other broader cognitive functions. However, older adults with mild cognitive decline who took matcha did show improvement in social cognition and sleep.
The study findings appear in PLOS ONE .
Matcha green tea is high in vitamins and minerals, including vitamins C and E, magnesium, and potassium. Matcha also has bioactive compounds, such as theanine and catechins.
Theanine is an amino acid in different foods and beverages that can help relax the mind. Catechins are polyphenols and can suppress inflammation in the body and prevent cell damage.
The researchers who conducted the current study examined how matcha impacts cognitive functioning by recruiting 99 participants and observing them for 12 months. The participants were aged 60 to 85.
Of the participants, 64 reported subjective cognitive decline, and 35 reported mild cognitive impairment . Participants were randomly assigned to the matcha or placebo group using a computer-generated system, ensuring a balance based on age (74 and older, or younger than 74), and apolipoprotein E (APOE) genotype , which is indicative of dementia risk.
The matcha group took 2 grams of green tea via a capsule daily while the placebo group took a capsule with corn starch.
This method aimed to evenly distribute these characteristics between the groups to minimize differences in dementia risk, especially because the 10-year Alzheimer’s disease risk is higher in people over 74 than those who are younger.
According to the researchers, the matcha capsules contained the following properties: 170.8 milligrams (mg) of catechins
48.1 mg of theanine
66.2 mg of caffeine per daily serving.
The researchers administered cognitive assessments at the beginning, end, and 6 months after the study intervention, including the Montreal Cognitive Assessment-Japanese version (MoCA-J) and Alzheimer’s Disease Cooperative Study Activity of Daily Living (ADCS-MCI-ADL).
They also tested the participants’ neuropsychological status, memory, executive functioning, attention, social acuity, and sleep quality.
Additionally, the researchers conducted neuroimaging at the baseline and end of the study to check the participants’ gray and white matter levels in their brains.
The scientists monitored the participants regularly throughout the 12 months. After the baseline visit, they saw the participants every 3 months until the end of the study intervention to assess their cognitive functioning levels.
The researchers noted having a high adherence rate in both the placebo and test groups. They said the participants in the test group had a higher blood level of theanine, which did not occur in the placebo group.
While the scientists expected the participants in the test group to show improvement in broader cognitive functioning by the end of the study, the test group did not show improvement compared to the placebo group.
Even when considering the neuroimaging, the participants taking matcha did not show improvements.
While the test group did not experience significant benefits where memory or executive functioning was concerned, the scientists did note improvements in sleep and social acuity in the test group. The results showed that the matcha group had significantly improved social acuity in the neurocognitive domain scores and showed a trend toward improved sleep quality after 12 months, although other cognitive functions did not show significant changes compared to the placebo group.Getting a good night’s sleep is important especially for older adults to stay physically and mentally healthy. The scientists think the theanine in matcha contributed to improved sleep quality.Since poor sleep is connected with increasing the risk of developing dementia and can negatively impact memory , the study results may be beneficial for people concerned about their sleep quality. The researchers found the improvements in social acuity scores in the test group promising. Participants in this group showed improvements in recognizing facial expressions and understanding word meanings. Not only is poor social communication an early indicator of dementia, but the social difficulties caused by dementia can be especially stressful. The improvement in social acuity needs to be further explored so providers can determine whether matcha is something to focus on in a clinical setting. Ralph Waldo, MD , an integrative medicine practitioner with HolistiqMD based in Indiana, spoke with Medical News Today about the study. Waldo was not involved in the research.“As a physician focused on root cause medicine, I have found matcha green tea intriguing for supporting cognitive health,” said Waldo. “The high theanine content is likely key for the sleep benefits seen in this study. Theanine reduces anxiety and stress, allowing for deeper sleep — essential for memory and focus, especially as we age.”Waldo also discussed how the catechins in matcha green tea may have improved the test group’s social acuity. “The catechins in matcha may protect social cognition specifically by decreasing inflammation in the brain and stimulating new neural connections,” he explained. “Matcha appears to target specific cognitive domains, as broader cognitive tests showed no change.” Waldo did note, however that more studies are needed to explore exactly how matcha benefits people.“More sensitive neuropsychological testing and biomarker analyses are […]
Cognitive behavioral therapy enhances brain circuits to relieve depression
Cognitive behavioral therapy, one of the most common treatments for depression, can teach skills for coping with everyday troubles, reinforce healthy behaviors and counter negative thoughts. But can altering thoughts and behaviors lead to lasting changes in the brain?
New research led by Stanford Medicine has found that it can — if a therapy is matched with the right patients. In a study of adults with both depression and obesity — a difficult-to-treat combination — cognitive behavioral therapy that focused on problem solving reduced depression in a third of patients. These patients also showed adaptative changes in their brain circuitry.
Moreover, these neural adaptations were apparent after just two months of therapy and could predict which patients would benefit from long-term therapy.
The findings add to evidence that choosing treatments based on the neurological underpinnings of a patient’s depression — which vary among people — increases the odds of success.
The same concept is already standard practice in other medical specialties.
“If you had chest pain, your physician would suggest some tests — an electrocardiogram, a heart scan, maybe a blood test — to work out the cause and which treatments to consider,” said Leanne Williams, PhD, the Vincent V.C. Woo Professor, a professor of psychiatry and behavioral sciences, and the director of Stanford Medicine’s Center for Precision Mental Health and Wellness.
“Yet in depression, we have no tests being used. You have this broad sense of emotional pain, but it’s a trial-and-error process to choose a treatment, because we have no tests for what is going on in the brain.”
Williams and Jun Ma, MD, PhD, professor of academic medicine and geriatrics at the University of Illinois at Chicago, are co-senior authors of the study published Sept. 4 in Science Translational Medicine. The work is part of a larger clinical trial called RAINBOW (Research Aimed at Improving Both Mood and Weight).
Problem solving
The form of cognitive behavioral therapy used in the trial, known as problem-solving therapy, is designed to improve cognitive skills used in planning, troubleshooting and tuning out irrelevant information. A therapist guides patients in identifying real-life problems — a conflict with a roommate, say — brainstorming solutions and choosing the best one.
These cognitive skills depend on a particular set of neurons that function together, known as the cognitive control circuit.
Previous work from Williams’ lab, which identified six biotypes of depression based on patterns of brain activity, estimated that a quarter of people with depression have dysfunction with their cognitive control circuits — either too much or too little activity.
The participants in the new study were adults diagnosed with both major depression and obesity, a confluence of symptoms that often indicates problems with the cognitive control circuit. Patients with this profile generally do poorly on antidepressants: They have a dismal response rate of 17%.
Of the 108 participants, 59 underwent a year-long program of problem-solving therapy in addition to their usual care, such as medications and visits to a primary care physician. The other 49 received only usual care.
They were given fMRI brain scans at the beginning of the study, then after two months, six months, 12 months and 24 months. During the brain scans, the participants completed a test that involves pressing or not pressing a button according to text on a screen — a task known to engage the cognitive control circuit. The test allowed the researchers to gauge changes in the activity of that circuit throughout the study.
“We wanted to see whether this problem-solving therapy in particular could modulate the cognitive control circuit,” said Xue Zhang, PhD, a postdoctoral scholar in psychiatry who is the lead author of the study.
With each brain scan, participants also filled out standard questionnaires that assessed their problem-solving ability and depression symptoms.
Working smarter
As with any other depression treatment, problem-solving therapy didn’t work for everyone. But 32% of participants responded to the therapy, meaning their symptom severity decreased by half or more.
“That’s a huge improvement over the 17% response rate for antidepressants,” Zhang said.
When researchers examined the brain scans, they found that in the group receiving only usual care, a cognitive control circuit that became less active over the course of the study correlated with worsening problem-solving ability.
But in the group receiving therapy, the pattern was reversed: Decreased activity correlated with enhanced problem-solving ability. The researchers think this may be due to their brains learning, through the therapy, to process information more efficiently.
“We believe they have more efficient cognitive processing, meaning now they need fewer resources in the cognitive control circuit to do the same behavior,” Zhang said.
Before the therapy, their brains had been working harder; now, they were working smarter.
Both groups, on average, improved in their overall depression severity. But when Zhang dug deeper into the 20-item depression assessment, she found that the depression symptom most relevant to cognitive control — “feeling everything is an effort” — benefited from the more efficient cognitive processing gained from the therapy.
“We’re seeing that we can pinpoint the improvement specific to the cognitive aspect of depression, which is what drives disability because it has the biggest impact on real-world functioning,” Williams said.Indeed, some participants reported that problem-solving therapy helped them think more clearly, allowing them to return to work, resume hobbies and manage social interactions. Fast track to recovery Just two months into the study, brain scans showed changes in cognitive control circuit activity in the therapy group.”That’s important, because it tells us that there is an actual brain change going on early, and it’s in the time frame that you’d expect brain plasticity,” Williams said. “Real-world problem solving is literally changing the brain in a couple of months.”The idea that thoughts and behaviors can modify brain circuits is not so different from how exercise — a behavior — strengthens muscles, she added.The researchers found that these early changes signaled which patients were responding to the therapy and would likely improve on problem-solving skills and depression symptoms at six months, 12 months and even one year after the therapy ended, at 24 months. That means a brain scan […]
Diversity nutritionist says unprocessed whole foods are RACIST
09/05/2024 // Ethan Huff // Views
Tags: #nutrition , absurd , badfood , badhealth , Crybullies , culture wars , diabetes , disease causes , food , frankenfood , identity politics , Jessica Wilson , junk food , junk science , nutrients , race relations , race war , race wars , racism , science deception , unprocessed , Whole Foods A “Queer. Black. Fat-positive dietitian” from California is on a mission to stop the war on ultra-processed food because she believes that opposing junk food means opposing “people of color” (POC).
Jessica Wilson, MS, RD, has apparently convinced herself that unhealthy eating is a normal part of being a POC, and that those who suggest healthier whole food-based diets are guilty of racism.
TIME wrote a piece about how Wilson was irked by the 2023 release of Ultra-Processed People , a book by Dr. Chris van Tulleken that highlighted how a junk food diet wrecked his health.
“What happened to me is exactly what the research says would happen to everyone,” van Tulleken wrote about how his health declined after switching to a diet mostly composed of chips, soda pop, bagged bread, frozen food and cereal.
Eating all that junk caused van Tulleken to feel sluggish and gain weight. His hormone levels got thrown all out of whack and MRI scans showed that even his brain got damaged.
Wilson, however, feels as though van Tulleken is exaggerating and over-sensationalizing what the junk food did to his body because she feels that processed foods are a normal part of people’s lives, as least the lives of POC whom she says tend to eat more junk food than white people.
Non-whites tend to have lower incomes and live in “food deserts” where there are fewer grocery stores carrying fresh produce and a whole lot more fast-food joints that serve fried, ultra-processed food-like substances.
Wilson claims that this differentiation between healthy foods and unhealthy foods is a form of “food apartheid” that makes no sense to her.
“How can this entire category of foods be something we’re supposed to avoid?” she asked.
(Related: Remember when Joe Biden tried to ban data for being “racist,” claiming that information all by itself is a form of white supremacy?) Full meals of ultra-processed foods made Wilson feel better
Wilson conducted her own experiment to contrast with that of van Tulleken. She traded out her haphazard attempts at eating whole foods randomly throughout the day with set meals comprised of more ultra-processed things.
Instead of eating morning eggs, for instance, Wilson opted for soy chorizo. She also swapped out of homemade “thrown-together” lunches with Trader Joe’s ready-to-eat tamales. Then there was the cashew “milk” yogurt with jam, Costco pupusas, and chicken sausage with veggies.
After making the switch to a more ultra-processed diet, Wilson claims she started to feel better with less anxiety and more energy. She drank less coffee and felt better than she had before, which she attributes to eating full meals with more calories.
Unlike van Tulleken, Wilson did not get any bloodwork done to see what her dietary changes did to her body. She simply reported that she “felt better” after doing her experiment.
“I finally understand where this sudden push in defense of ultra-processed foods comes from: the desire of the psychopaths to replace meat and other healthy foods with fake products,” one commenter wrote.
“The obvious criticism would be that such artificial food-like products are ultra-processed garbage, and thus ultra-processed foods suddenly have to become ‘healthy.’ Duh.”
The other obvious answer as to why ultra-processed food is suddenly in vogue among the pro-fat crowd is because it is cheap and generates large profits for the same multinational corporate interests that came up with the so-called “food pyramid.”
“This is to keep the masses sick and weak,” wrote another.
“Four out of five eugenicists surveyed prefer ultra-processed foods,” joked another. “The fifth died from myocarditis.”
In 2024, anything and everything is “racist.” Learn more at RaceWar.news .
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Novel Drug Shows Promise in Preventing Early Alzheimer’s Brain Changes
Summary: A recent study has shown that troriluzole can prevent early-stage brain changes in a mouse model of Alzheimer’s disease. The research demonstrated that troriluzole reduces harmful glutamate levels, preserving memory and cognitive function.
This breakthrough suggests that early intervention with troriluzole could slow or even halt the progression of Alzheimer’s, offering new hope for potential treatments. However, further studies are necessary to determine its effectiveness across different stages of the disease.
Key Facts: Troriluzole reduces harmful glutamate levels, protecting brain function.
Mice treated with troriluzole showed improved memory and learning abilities.
Further research is needed to explore troriluzole’s effects across all stages of Alzheimer’s.
Source: Auburn University
In a recent development in Alzheimer’s disease research, Auburn University scientists have studied a new drug, troriluzole, that can prevent brain changes leading to memory loss and cognitive decline in a mouse model of the disease.
This study, recently published in the Journal of Neurochemistry , is the first to show how troriluzole can target early-stage alterations associated with Alzheimer’s, providing new hope for potential treatments.
Dr. Miranda Reed, a Professor in the department of Drug Discovery at Auburn University and Delivery and the studies main researcher, noted that “by examining how drug treatments can intervene early in the disease process, we aim to develop therapies that might prevent or even cure Alzheimer’s.” In the Auburn study, mice treated with troriluzole showed a significant reduction in synaptic glutamate levels and decreased brain hyperactivity. Credit: Neuroscience News “This study also highlights how scientific advancements can transform our understanding of complex diseases like Alzheimer’s,” said Dr. Michael Gramlich, an Assistant Professor of Biophysics and the study’s other main researcher.
Breaking New Ground in Alzheimer’s Research
Alzheimer’s disease affects millions of people worldwide, causing progressive memory loss, confusion, and eventually the inability to perform basic tasks. Despite decades of research, a cure remains elusive. Alzheimer’s is characterized by the accumulation of amyloid plaques and tau tangles in the brain, which disrupt neural communication. In the early stages, excessive levels of the neurotransmitter glutamate cause damaging overactivity in synapses, the connections between nerve cells.
The study conducted by Auburn University researchers, led by Drs. Miranda Reed and Michael Gramlich, investigated how troriluzole, a novel drug, can maintain normal brain function in mice genetically modified to replicate early Alzheimer’s stages. The results are compelling: troriluzole not only reduced harmful glutamate levels but also improved memory and learning in the mice, suggesting a maintenance of healthy brain function.
“Our research demonstrates that by targeting synaptic activity early, we may be able to prevent or slow the progression of Alzheimer’s. This could revolutionize the way we approach treatment for this disease,” noted both researchers.
How Troriluzole Works
In the Auburn study, mice treated with troriluzole showed a significant reduction in synaptic glutamate levels and decreased brain hyperactivity. These molecular changes led to tangible improvements: the treated mice performed better in memory tests, such as navigating mazes, indicating that their cognitive functions were restored.
“These findings are promising because they suggest that troriluzole can protect the brain at a fundamental level, starting with molecular changes and resulting in improved cognitive abilities,” said Dr. Reed. “It’s like repairing an engine before it fails completely.”
A Collaborative Effort with Wide Implications
This research was a collaborative effort involving Auburn University’s College of Science and Mathematics, the Harrison College of Pharmacy, and the Center for Neuroscience Initiative, along with private researchers and students. The team’s combined expertise in neuroscience and pharmacology was crucial to the study’s success.
“This collaboration blends basic science and pharmaceutical research to tackle one of the most challenging neurological issues of our time,” Dr. Gramlich emphasized. “Our work not only enhances scientific understanding of Alzheimer’s disease but also offers a potential new treatment that could improve the lives of millions worldwide.”
What’s Next?
While the results in mice are encouraging, the researchers emphasize the need for further studies to determine how troriluzole works at different stages of disease progression. About this neuropharmacology and Alzheimer’s disease research news
Author: Mary Prater
Source: Auburn University
Contact: Mary Prater – Auburn University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“ Troriluzole rescues glutamatergic deficits, amyloid and tau pathology, and synaptic and memory impairments in 3xTg-AD mice ” by Michael Gramlich et al. Journal of Neurochemistry
Abstract Troriluzole rescues glutamatergic deficits, amyloid and tau pathology, and synaptic and memory impairments in 3xTg-AD mice Alzheimer’s disease (AD) is a neurodegenerative condition in which clinical symptoms are highly correlated with the loss of glutamatergic synapses. While later stages of AD are associated with markedly decreased glutamate levels due to neuronal loss, in the early stages, pathological accumulation of glutamate and hyperactivity contribute to AD pathology and cognitive dysfunction.There is increasing awareness that presynaptic dysfunction, particularly synaptic vesicle (SV) alterations, play a key role in mediating this early-stage hyperactivity.In the current study, we sought to determine whether the 3xTg mouse model of AD that exhibits both beta-amyloid (Aβ) and tau-related pathology would exhibit similar presynaptic changes as previously observed in amyloid or tau models separately.Hippocampal cultures from 3xTg mice were used to determine whether presynaptic vesicular glutamate transporters (VGlut) and glutamate are increased at the synaptic level while controlling for postsynaptic activity.We observed that 3xTg hippocampal cultures exhibited increased VGlut1 associated with an increase in glutamate release, similar to prior observations in cultures from tau mouse models.However, the SV pool size was also increased in 3xTg cultures, an effect not previously observed in tau mouse models but observed in Aβ models, suggesting the changes in pool size may be due to Aβ and not tau.Second, we sought to determine whether treatment with troriluzole, a novel 3rd generation tripeptide prodrug of the glutamate modulator riluzole, could reduce VGlut1 and glutamate release to restore cognitive deficits in 8-month-old 3xTg mice.Treatment with troriluzole reduced VGlut1 expression, decreased basal and evoked glutamate release, and restored cognitive deficits in 3xTg mice.Together, these findings suggest presynaptic alterations are early events in AD that represent potential targets for therapeutic […]
RNA treatment shows promise for enhancing memory and reducing anxiety
Targeting strategy to knock down the mouse HTR2A gene using shRNA and transduction efficiency in primary mouse cortical neurons. Credit: Genomic Psychiatry (2024). DOI: 10.61373/gp024r.0043 Scientists at Cognigenics have made a significant advance in the field of neuroscience and mental health treatment. Their research, published in Genomic Psychiatry , demonstrates that a new RNA-based therapy called COG-201 can enhance memory and reduce anxiety in animal models.
COG-201 uses short hairpin RNA (shRNA) to target and reduce the expression of the serotonin 5-HT2A receptor in the brain. This receptor plays a crucial role in regulating mood, anxiety, and cognitive functions. By decreasing its expression, the researchers observed notable improvements in memory and reductions in anxiety-like behaviors in both mice and rats.
“Our findings suggest that COG-201 could offer a new approach to treating conditions like mild cognitive impairment and anxiety disorders ,” said Dr. Troy T. Rohn, lead author of the study. “What’s particularly exciting is that we’re seeing these effects through a non-invasive, intranasal delivery method.”
The study provides both behavioral and neurophysiological evidence for the efficacy of COG-201. In addition to improved performance on memory tests, treated animals showed changes in neuronal activity that aligned with enhanced cognitive function. Specifically, the researchers observed decreased spontaneous electrical activity in cortical neurons , suggesting a reduction in overall neural excitability.
This research represents a significant step forward in the development of precision-based therapeutics for neurological and psychiatric disorders . By targeting a specific receptor with RNA interference, COG-201 offers a more precise approach compared to traditional pharmacological treatments.
“We’re particularly encouraged by the potential applications for patients with mild cognitive impairment who also experience anxiety,” noted Dr. Fabio Macciardi, a co-author of the study. “Currently, there’s no single medication that effectively addresses both of these symptoms.”
While the results are promising, the researchers caution that further studies, including trials in larger animals and eventually humans, will be necessary to fully understand the therapy’s potential and safety profile.
This innovative approach to treating cognitive and mood disorders could open new avenues for therapeutic interventions. As the global population ages and the prevalence of cognitive impairments increases, therapies like COG-201 may offer hope for millions of people worldwide.
More information: Troy T. Rohn et al, Treatment with shRNA to knockdown the 5-HT2A receptor improves memory in vivo and decreases excitability in primary cortical neurons, Genomic Psychiatry (2024). DOI: 10.61373/gp024r.0043 . gp.genomicpress.com/wp-content … GP0043-Rohn-2024.pdf
Provided by Genomic Press
New study reveals the signals in your brain that initiate spontaneous actions
by Chapman University Credit: Unsplash/CC0 Public Domain A new study published in Nature Communications examines how the brain initiates spontaneous actions. In addition to demonstrating how spontaneous action emerges without environmental input, this research has implications for the origins of slow ramping of neural activity before movement onset—a commonly-observed but poorly understood phenomenon.
The study was led by Jake Gavenas, Ph.D., while he was a Ph.D. student at the Brain Institute at Chapman University, and co-authored by two faculty members of the Brain Institute, Uri Maoz and Aaron Schurger. In their work, the researchers propose an answer to that question. They simulated spontaneous activity in simple neural networks and compared this simulated activity to intracortical recordings of humans when they moved spontaneously.
The study results suggest something striking: Many rapidly fluctuating neurons can interact in a network to give rise to very slow fluctuations at the level of the neuron population.
Imagine, for example, standing atop a high-dive platform and trying to summon the willpower to jump. Nothing in the outside world tells you when to jump; that decision comes from within. At some point you experience deciding to jump and then you jump.
In the background, your brain (or more specifically, your motor cortex) sends electrical signals that cause carefully coordinated muscle contractions across your body, resulting in you running and jumping. But where in the brain do these signals originate, and how do they relate to the conscious experience of willing your body to move?
Starting from the 1960s, neuroscientists have found that electrical activity in the brain ramps up one to two seconds before spontaneous voluntary actions. Many scientists thought that the onset of this ramping reflected preparation to move following a preconscious decision to act. But, despite investigations into the origins of this slowly ramping activity, it seemed as though it suddenly emerged “out of nowhere.”
In the years since, neuroscientists and philosophers have debated what this ramping means for free will and conscious self-control. If, following an early decision to move, the brain is preparing to move two seconds (or more, according to some studies) before you consciously decide to move, might your actions be largely unconsciously predetermined? Understanding the neural origin of this ramping activity is therefore a paramount problem in neuroscience.
The view that there is preconscious information in the brain seconds before action onset has been challenged by neuroscientists like Maoz and Schurger.
In particular, in 2012, Schurger suggested that the slow ramping brain activity is part of a larger process, in which slow background fluctuations in motor-cortex activity must reach a certain threshold to initiate movement.
If those slow fluctuations help to determine the moment of threshold crossing, then looking back from movement onset ensures that you will observe slow ramping beforehand, even if the ramping is not the outcome of an early preconscious decision to move. In this view, the important event is not the onset of the slow-ramping process but instead the crossing of the threshold.
Although compelling, this explanation leaves a key unanswered question: where do these slow background fluctuations in neural activity–commonly known as 1/f noise–come from in the first place, given that the activity of individual neurons fluctuates quite rapidly?
This study is the first to explain how those slow background fluctuations emerge from networks of neurons, where none of the individual neurons by themselves operate on that long of a time-scale. Those slow fluctuations may then, in turn, contribute to a threshold-crossing event, of the kind that is thought to trigger movement, and thus to the slow ramping that is evident before spontaneous action onset and beyond.
Gavenas said, “We see similar slow-ramping signals before other kinds of spontaneous behaviors, like coming up with creative ideas or freely remembering things that have happened to you. A similar process might therefore underlie those phenomena, but only time and further research will tell.”
In sum, this is a landmark study because it offers a potential explanation for the origin of slow, spontaneous fluctuations in population-level neural activity, which is a ubiquitous phenomenon in neural systems.
In addition, according to Maoz, “It reveals the bias we have as researchers to think that our results uncover a causal mechanism, when it may really be just a correlation.”
More information: Jake Gavenas et al, Slow ramping emerges from spontaneous fluctuations in spiking neural networks, Nature Communications (2024). DOI: 10.1038/s41467-024-51401-x
Provided by Chapman University
RNA Therapy Improves Memory and Reduces Anxiety
Summary: An RNA-based therapy, COG-201, can enhance memory and reduce anxiety in animal models by targeting the serotonin 5-HT2A receptor. Scientists found that decreasing this receptor’s expression led to improved cognitive function and reduced anxiety-like behaviors in mice and rats.
Notably, the therapy is delivered non-invasively via an intranasal method, making it a promising treatment for conditions like mild cognitive impairment and anxiety. Further studies are required to assess its safety and efficacy in humans.
Key Facts: COG-201 targets the serotonin 5-HT2A receptor to improve memory and reduce anxiety.
The therapy is delivered non-invasively through an intranasal method.
Animal studies showed improved cognitive performance and reduced neural excitability.
Source: Genomic Press
Scientists at Cognigenics have made a significant advance in the field of neuroscience and mental health treatment.
Their groundbreaking research, published in Genomic Psychiatry , demonstrates that a new RNA-based therapy called COG-201 can enhance memory and reduce anxiety in animal models. This research represents a significant step forward in the development of precision-based therapeutics for neurological and psychiatric disorders. Credit: Neuroscience News COG-201 uses short hairpin RNA (shRNA) to target and reduce the expression of the serotonin 5-HT2A receptor in the brain. This receptor plays a crucial role in regulating mood, anxiety, and cognitive functions.
By decreasing its expression, the researchers observed notable improvements in memory and reductions in anxiety-like behaviors in both mice and rats.
“Our findings suggest that COG-201 could offer a new approach to treating conditions like mild cognitive impairment and anxiety disorders,” said Dr. Troy T. Rohn, lead author of the study.
“What’s particularly exciting is that we’re seeing these effects through a non-invasive, intranasal delivery method.”
The study provides both behavioral and neurophysiological evidence for the efficacy of COG-201. In addition to improved performance on memory tests, treated animals showed changes in neuronal activity that align with enhanced cognitive function.
Specifically, the researchers observed decreased spontaneous electrical activity in cortical neurons, suggesting a reduction in overall neural excitability.
This research represents a significant step forward in the development of precision-based therapeutics for neurological and psychiatric disorders. By targeting a specific receptor with RNA interference, COG-201 offers a more precise approach compared to traditional pharmacological treatments.
“We’re particularly encouraged by the potential applications for patients with mild cognitive impairment who also experience anxiety,” noted Dr. Fabio Macciardi, a co-author of the study.
“Currently, there’s no single medication that effectively addresses both of these symptoms.”
While the results are promising, the researchers caution that further studies, including trials in larger animals and eventually humans, will be necessary to fully understand the therapy’s potential and safety profile.
This innovative approach to treating cognitive and mood disorders could open new avenues for therapeutic interventions. As the global population ages and the prevalence of cognitive impairments increases, therapies like COG-201 may offer hope for millions of people worldwide. About this genetics, memory, and anxiety research news
Author: Ma-Li Wong
Source: Genomic Press
Contact: Ma-Li Wong – Genomic Press
Image: The image is credited to Neuroscience News
Original Research: Open access.
“ Treatment with shRNA to knockdown the 5-HT2A receptor improves memory in vivo and decreases excitability in primary cortical neurons ” by Troy T. Rohn et al. Genomic Psychiatry
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This metabolic brain boost revives memory in Alzheimer’s mice
Aging and Alzheimer’s leave the brain starved of energy. Now scientists think they’ve found a way to aid the brain’s metabolism — in mice. An experimental cancer drug that helps the brain turn glucose into energy was able to reverse memory loss in a mouse model of Alzheimer’s disease.
The brain needs a lot of energy — far more than any other organ in the body — to work properly. And aging and Alzheimer’s disease both seem to leave the brain underpowered.
But an experimental cancer drug appeared to re-energize the brains of mice that had a form of Alzheimer’s — and even restore their ability to learn and remember.
The finding, published in the journal Science , suggests that it may eventually be possible to reverse some symptoms of Alzheimer’s in people, using drugs that boost brain metabolism.
The results also offer an approach to treatment that’s unlike anything on the market today. Current drugs for treating Alzheimer’s, such as lecanemab and donanemab, target the sticky amyloid plaques that build up in a patient’s brain. These drugs can remove plaques and slow the disease process, but do not improve memory or thinking.
The result should help “change how we think about targeting this disease,” says Shannon Macauley , an associate professor at the University of Kentucky who was not involved in the study. A surprise, then a discovery
The new research was prompted by a lab experiment that didn’t go as planned.
A team at Stanford was studying an enzyme called IDO1 that plays a key role in keeping a cell’s metabolism running properly. They suspected that in Alzheimer’s disease, IDO1 was malfunctioning in a way that limited the brain’s ability to turn nutrients into energy.
So the team used genetics to eliminate the enzyme entirely from mice that develop a form of Alzheimer’s. They figured that without any IDO1, brain metabolism would decline.
“We expected to see everything [get] much, much, much worse”, says Dr. Katrin Andreasson , a professor of neurology and neuroscience at Stanford. “But no, it was the complete opposite.”
Without the enzyme, the mouse brains were actually better at turning glucose into energy and didn’t exhibit the memory loss usually associated with Alzheimer’s.
“It was such a profound rescue that we sort of went back to the drawing board and tried to figure out what was going on,” Andreasson says.
Eventually, the team found an explanation.
Getting rid of the enzyme had altered the behavior of cells called astrocytes.
Usually, astrocytes help provide energy to neurons, the cells that allow for learning and memory. But when the toxic plaques and tangles of Alzheimer’s begin to appear in the brain, levels of IDO1 rise and astrocytes stop doing this job.
“They’re kind of put to sleep,” Andreasson says. So “you’ve got to wake them up to get them to help the neurons.”
And that’s what happened when scientists used genetics to remove IDO1.
Their hypothesis was that high levels of IDO1 were limiting the astrocytes’ ability to produce lactate, a chemical that helps brain cells, including neurons, transform food into energy.
To confirm the hypothesis, the team, led by Dr. Paras Minhas , did a series of experiments. One involved placing a mouse in the center of a shiny white disk under a bright light.
“It really wants to get out of there,” Andreasson says. “But it has to learn where the escape hole is” by following visual cues.
Healthy mice learned how to read those cues after a few days of training, and would escape almost instantly.
“But in the Alzheimer mice, the time to find the escape hole really skyrocketed,” Andreasson says.
That changed when the team gave these mice an experimental cancer drug that could block the enzyme much the way genetic engineering had.
The treated mice learned to escape the bright light as quickly as healthy animals. And a look at their brains showed that their astrocytes had woken up and were helping neurons produce the energy needed for memory and thinking.
In the hippocampus, a brain area that’s critical for memory and navigation, tests showed that the drug had restored normal glucose metabolism even though the plaques and tangles of Alzheimer’s were still present.
The team also tested human astrocytes and neurons derived from Alzheimer’s patients. And once again, the drug restored normal function. Beyond plaques and tangles The experiments add to the evidence that Alzheimer’s involves a lot more than just the appearance of plaques and tangles.“We can have these metabolic changes in our brain,” Macaulay says, “but they’re reversible.”Neurons have long been the focus of Alzheimer’s research. But the new results also show how other kinds of cells in the brain can play an important role in the disease.The brain is a bit like a beehive, where a neuron is the queen, Macaulay says. But she’s kept alive by worker bees, like astrocytes, which are asked to do more as Alzheimer’s changes the brain.“Those worker bees are getting unbelievably taxed from all the things they are being asked to do,” Macaulay says. “When that happens, then the whole system doesn’t work well.”Metabolic treatments that restore astrocytes and other helper cells in the brain could someday augment existing Alzheimer’s drugs that remove amyloid plaques, Macauley says.And the metabolic approach may be able to improve memory and thinking — something amyloid drugs don’t do.“Maybe this can make your astrocytes and your neurons work a little bit better, so that you function a little bit better,” Macaulay says.But first, she says, the promising results will have to be replicated in people.Copyright 2024 NPRTags NPR News NPR Featured Facebook Twitter LinkedIn Email Jon HamiltonJon Hamilton is a correspondent for NPR’s Science Desk. Currently he focuses on neuroscience and health risks.
This metabolic brain boost revives memory in Alzheimer’s mice
Aging and Alzheimer’s leave the brain starved of energy. Now scientists think they’ve found a way to aid the brain’s metabolism — in mice. The brain needs a lot of energy — far more than any other organ in the body — to work properly. And aging and Alzheimer’s disease both seem to leave the brain underpowered.
But an experimental cancer drug appeared to re-energize the brains of mice that had a form of Alzheimer’s — and even restore their ability to learn and remember.
The finding, published in the journal Science , suggests that it may eventually be possible to reverse some symptoms of Alzheimer’s in people, using drugs that boost brain metabolism.
The results also offer an approach to treatment that’s unlike anything on the market today. Current drugs for treating Alzheimer’s, such as lecanemab and donanemab, target the sticky amyloid plaques that build up in a patient’s brain. These drugs can remove plaques and slow the disease process, but do not improve memory or thinking.
The result should help “change how we think about targeting this disease,” says Shannon Macauley , an associate professor at the University of Kentucky who was not involved in the study. A surprise, then a discovery
The new research was prompted by a lab experiment that didn’t go as planned.
A team at Stanford was studying an enzyme called IDO1 that plays a key role in keeping a cell’s metabolism running properly. They suspected that in Alzheimer’s disease, IDO1 was malfunctioning in a way that limited the brain’s ability to turn nutrients into energy.
So the team used genetics to eliminate the enzyme entirely from mice that develop a form of Alzheimer’s. They figured that without any IDO1, brain metabolism would decline.
“We expected to see everything [get] much, much, much worse”, says Dr. Katrin Andreasson , a professor of neurology and neuroscience at Stanford. “But no, it was the complete opposite.”
Without the enzyme, the mouse brains were actually better at turning glucose into energy and didn’t exhibit the memory loss usually associated with Alzheimer’s.
“It was such a profound rescue that we sort of went back to the drawing board and tried to figure out what was going on,” Andreasson says.
Eventually, the team found an explanation.
Getting rid of the enzyme had altered the behavior of cells called astrocytes.
Usually, astrocytes help provide energy to neurons, the cells that allow for learning and memory. But when the toxic plaques and tangles of Alzheimer’s begin to appear in the brain, levels of IDO1 rise and astrocytes stop doing this job.
“They’re kind of put to sleep,” Andreasson says. So “you’ve got to wake them up to get them to help the neurons.”
And that’s what happened when scientists used genetics to remove IDO1.
Their hypothesis was that high levels of IDO1 were limiting the astrocytes’ ability to produce lactate, a chemical that helps brain cells, including neurons, transform food into energy.
To confirm the hypothesis, the team, led by Dr. Paras Minhas , did a series of experiments. One involved placing a mouse in the center of a shiny white disk under a bright light.
“It really wants to get out of there,” Andreasson says. “But it has to learn where the escape hole is” by following visual cues.
Healthy mice learned how to read those cues after a few days of training, and would escape almost instantly.
“But in the Alzheimer mice, the time to find the escape hole really skyrocketed,” Andreasson says.
That changed when the team gave these mice an experimental cancer drug that could block the enzyme much the way genetic engineering had.
The treated mice learned to escape the bright light as quickly as healthy animals. And a look at their brains showed that their astrocytes had woken up and were helping neurons produce the energy needed for memory and thinking.
In the hippocampus, a brain area that’s critical for memory and navigation, tests showed that the drug had restored normal glucose metabolism even though the plaques and tangles of Alzheimer’s were still present.
The team also tested human astrocytes and neurons derived from Alzheimer’s patients. And once again, the drug restored normal function. Beyond plaques and tangles
The experiments add to the evidence that Alzheimer’s involves a lot more than just the appearance of plaques and tangles.“We can have these metabolic changes in our brain,” Macaulay says, “but they’re reversible.”Neurons have long been the focus of Alzheimer’s research. But the new results also show how other kinds of cells in the brain can play an important role in the disease.The brain is a bit like a beehive, where a neuron is the queen, Macaulay says. But she’s kept alive by worker bees, like astrocytes, which are asked to do more as Alzheimer’s changes the brain.“Those worker bees are getting unbelievably taxed from all the things they are being asked to do,” Macaulay says. “When that happens, then the whole system doesn’t work well.”Metabolic treatments that restore astrocytes and other helper cells in the brain could someday augment existing Alzheimer’s drugs that remove amyloid plaques, Macauley says.And the metabolic approach may be able to improve memory and thinking — something amyloid drugs don’t do.“Maybe this can make your astrocytes and your neurons work a little bit better, so that you function a little bit better,” Macaulay says.But first, she says, the promising results will have to be replicated in people.Copyright 2024 NPR From NPR Facebook Twitter LinkedIn Email Jon HamiltonJon Hamilton is a correspondent for NPR’s Science Desk. Currently he focuses on neuroscience and health risks.
This metabolic brain boost revives memory in Alzheimer’s mice
Aging and Alzheimer’s leave the brain starved of energy. Now scientists think they’ve found a way to aid the brain’s metabolism — in mice. The brain needs a lot of energy — far more than any other organ in the body — to work properly. And aging and Alzheimer’s disease both seem to leave the brain underpowered.
But an experimental cancer drug appeared to re-energize the brains of mice that had a form of Alzheimer’s — and even restore their ability to learn and remember.
The finding, published in the journal Science , suggests that it may eventually be possible to reverse some symptoms of Alzheimer’s in people, using drugs that boost brain metabolism.
The results also offer an approach to treatment that’s unlike anything on the market today. Current drugs for treating Alzheimer’s, such as lecanemab and donanemab, target the sticky amyloid plaques that build up in a patient’s brain. These drugs can remove plaques and slow the disease process, but do not improve memory or thinking.
The result should help “change how we think about targeting this disease,” says Shannon Macauley , an associate professor at the University of Kentucky who was not involved in the study. A surprise, then a discovery
The new research was prompted by a lab experiment that didn’t go as planned.
A team at Stanford was studying an enzyme called IDO1 that plays a key role in keeping a cell’s metabolism running properly. They suspected that in Alzheimer’s disease, IDO1 was malfunctioning in a way that limited the brain’s ability to turn nutrients into energy.
So the team used genetics to eliminate the enzyme entirely from mice that develop a form of Alzheimer’s. They figured that without any IDO1, brain metabolism would decline.
“We expected to see everything [get] much, much, much worse”, says Dr. Katrin Andreasson , a professor of neurology and neuroscience at Stanford. “But no, it was the complete opposite.”
Without the enzyme, the mouse brains were actually better at turning glucose into energy and didn’t exhibit the memory loss usually associated with Alzheimer’s.
“It was such a profound rescue that we sort of went back to the drawing board and tried to figure out what was going on,” Andreasson says.
Eventually, the team found an explanation.
Getting rid of the enzyme had altered the behavior of cells called astrocytes.
Usually, astrocytes help provide energy to neurons, the cells that allow for learning and memory. But when the toxic plaques and tangles of Alzheimer’s begin to appear in the brain, levels of IDO1 rise and astrocytes stop doing this job.
“They’re kind of put to sleep,” Andreasson says. So “you’ve got to wake them up to get them to help the neurons.”
And that’s what happened when scientists used genetics to remove IDO1.
Their hypothesis was that high levels of IDO1 were limiting the astrocytes’ ability to produce lactate, a chemical that helps brain cells, including neurons, transform food into energy.
To confirm the hypothesis, the team, led by Dr. Paras Minhas , did a series of experiments. One involved placing a mouse in the center of a shiny white disk under a bright light.
“It really wants to get out of there,” Andreasson says. “But it has to learn where the escape hole is” by following visual cues.
Healthy mice learned how to read those cues after a few days of training, and would escape almost instantly.
“But in the Alzheimer mice, the time to find the escape hole really skyrocketed,” Andreasson says.
That changed when the team gave these mice an experimental cancer drug that could block the enzyme much the way genetic engineering had.
The treated mice learned to escape the bright light as quickly as healthy animals. And a look at their brains showed that their astrocytes had woken up and were helping neurons produce the energy needed for memory and thinking.
In the hippocampus, a brain area that’s critical for memory and navigation, tests showed that the drug had restored normal glucose metabolism even though the plaques and tangles of Alzheimer’s were still present.
The team also tested human astrocytes and neurons derived from Alzheimer’s patients. And once again, the drug restored normal function. Beyond plaques and tangles
The experiments add to the evidence that Alzheimer’s involves a lot more than just the appearance of plaques and tangles.“We can have these metabolic changes in our brain,” Macaulay says, “but they’re reversible.”Neurons have long been the focus of Alzheimer’s research. But the new results also show how other kinds of cells in the brain can play an important role in the disease.The brain is a bit like a beehive, where a neuron is the queen, Macaulay says. But she’s kept alive by worker bees, like astrocytes, which are asked to do more as Alzheimer’s changes the brain.“Those worker bees are getting unbelievably taxed from all the things they are being asked to do,” Macaulay says. “When that happens, then the whole system doesn’t work well.”Metabolic treatments that restore astrocytes and other helper cells in the brain could someday augment existing Alzheimer’s drugs that remove amyloid plaques, Macauley says.And the metabolic approach may be able to improve memory and thinking — something amyloid drugs don’t do.“Maybe this can make your astrocytes and your neurons work a little bit better, so that you function a little bit better,” Macaulay says.But first, she says, the promising results will have to be replicated in people.Copyright 2024 NPRTags NPR Health NPR Top Stories Facebook Twitter LinkedIn Email
Reversing brain aging: New drug restores brain’s natural waste removal system
Credit: Unsplash+. Alzheimer’s, Parkinson’s, and other neurological diseases can be thought of as “dirty brain” conditions, where the brain struggles to clear out harmful waste.
As we age, our brain’s ability to remove toxic buildup slows down, increasing the risk of these diseases.
However, new research in mice has shown that it’s possible to reverse these age-related changes and restore the brain’s waste-clearing system.
Scientists at the University of Rochester have discovered that restoring the function of lymph vessels in the neck can significantly improve the brain’s ability to remove waste.
This breakthrough, achieved using a drug already in clinical use, offers hope for new treatment strategies for neurological disorders linked to aging.
The study, led by Dr. Douglas Kelley and Dr. Maiken Nedergaard, was published in the journal Nature Aging.
The brain has a unique waste removal system known as the glymphatic system. This system uses cerebrospinal fluid (CSF) to flush out excess proteins and other waste produced by the brain during normal activities.
In young and healthy brains, the glymphatic system efficiently clears away these toxic proteins, preventing their buildup.
However, as we age, the system becomes less effective, leading to the accumulation of harmful substances like beta-amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.
For the brain’s waste to be removed from the body, the cerebrospinal fluid carrying the waste must exit the skull and enter the lymphatic system. From there, it travels to the kidneys, where it is processed and eliminated from the body.
The researchers used advanced imaging techniques to map out how this waste-laden fluid leaves the brain. They discovered that about half of the dirty CSF exits through tiny lymph vessels in the neck.
These lymph vessels, which are lined with microscopic pumps called lymphangions, play a crucial role in transporting fluid.
Unlike the cardiovascular system, which relies on the heart to pump blood, the lymphatic system uses a series of small pumps to move fluid. Each lymphangion has valves that prevent backflow, ensuring that the waste-laden CSF is pushed out of the brain.
However, as the mice in the study aged, the researchers observed that the frequency of these lymphangion contractions decreased, and the valves began to fail.
As a result, the flow of dirty CSF out of the brain slowed down by 63% in older mice compared to younger ones.
To address this decline, the researchers explored whether they could revive the function of these lymphangions.
They identified a drug called prostaglandin F2α, a hormone-like compound commonly used to induce labor.
Prostaglandin F2α is known to help smooth muscle cells contract, and lymphangions are lined with these smooth muscle cells.
When the researchers applied the drug to the cervical lymph vessels in older mice, they found that it increased the frequency of lymphangion contractions and sped up the flow of dirty CSF from the brain. Remarkably, the efficiency of waste removal returned to levels seen in younger mice.
Dr. Kelley noted that the lymph vessels are conveniently located near the surface of the skin, making them accessible for potential treatments.
He suggested that this approach, possibly combined with other therapies, could be the foundation for future treatments aimed at improving brain health in older adults.
This research highlights the potential for using existing drugs to restore the brain’s natural waste removal system, offering hope for new ways to treat or even prevent neurological diseases associated with aging.
By improving the brain’s ability to clear out toxic proteins, we may be able to reduce the risk of developing conditions like Alzheimer’s and Parkinson’s, ultimately leading to healthier aging and better quality of life for millions of people.
If you care about brain health, please read studies that eating apples and tea could keep dementia at bay, and Olive oil: a daily dose for better brain health.
For more health information, please see recent studies what you eat together may affect your dementia risk, and time-restricted eating: a simple way to fight aging and cancer .
This metabolic brain boost revives memory in Alzheimer’s mice
Aging and Alzheimer’s leave the brain starved of energy. Now scientists think they’ve found a way to aid the brain’s metabolism — in mice. The brain needs a lot of energy — far more than any other organ in the body — to work properly. And aging and Alzheimer’s disease both seem to leave the brain underpowered.
But an experimental cancer drug appeared to re-energize the brains of mice that had a form of Alzheimer’s — and even restore their ability to learn and remember.
The finding, published in the journal Science , suggests that it may eventually be possible to reverse some symptoms of Alzheimer’s in people, using drugs that boost brain metabolism.
The results also offer an approach to treatment that’s unlike anything on the market today. Current drugs for treating Alzheimer’s, such as lecanemab and donanemab, target the sticky amyloid plaques that build up in a patient’s brain. These drugs can remove plaques and slow the disease process, but do not improve memory or thinking.
The result should help “change how we think about targeting this disease,” says Shannon Macauley , an associate professor at the University of Kentucky who was not involved in the study. A surprise, then a discovery
The new research was prompted by a lab experiment that didn’t go as planned.
A team at Stanford was studying an enzyme called IDO1 that plays a key role in keeping a cell’s metabolism running properly. They suspected that in Alzheimer’s disease, IDO1 was malfunctioning in a way that limited the brain’s ability to turn nutrients into energy.
So the team used genetics to eliminate the enzyme entirely from mice that develop a form of Alzheimer’s. They figured that without any IDO1, brain metabolism would decline.
“We expected to see everything [get] much, much, much worse”, says Dr. Katrin Andreasson , a professor of neurology and neuroscience at Stanford. “But no, it was the complete opposite.”
Without the enzyme, the mouse brains were actually better at turning glucose into energy and didn’t exhibit the memory loss usually associated with Alzheimer’s.
“It was such a profound rescue that we sort of went back to the drawing board and tried to figure out what was going on,” Andreasson says.
Eventually, the team found an explanation.
Getting rid of the enzyme had altered the behavior of cells called astrocytes.
Usually, astrocytes help provide energy to neurons, the cells that allow for learning and memory. But when the toxic plaques and tangles of Alzheimer’s begin to appear in the brain, levels of IDO1 rise and astrocytes stop doing this job.
“They’re kind of put to sleep,” Andreasson says. So “you’ve got to wake them up to get them to help the neurons.”
And that’s what happened when scientists used genetics to remove IDO1.
Their hypothesis was that high levels of IDO1 were limiting the astrocytes’ ability to produce lactate, a chemical that helps brain cells, including neurons, transform food into energy.
To confirm the hypothesis, the team, led by Dr. Paras Minhas , did a series of experiments. One involved placing a mouse in the center of a shiny white disk under a bright light.
“It really wants to get out of there,” Andreasson says. “But it has to learn where the escape hole is” by following visual cues.
Healthy mice learned how to read those cues after a few days of training, and would escape almost instantly.
“But in the Alzheimer mice, the time to find the escape hole really skyrocketed,” Andreasson says.
That changed when the team gave these mice an experimental cancer drug that could block the enzyme much the way genetic engineering had.
The treated mice learned to escape the bright light as quickly as healthy animals. And a look at their brains showed that their astrocytes had woken up and were helping neurons produce the energy needed for memory and thinking.
In the hippocampus, a brain area that’s critical for memory and navigation, tests showed that the drug had restored normal glucose metabolism even though the plaques and tangles of Alzheimer’s were still present.
The team also tested human astrocytes and neurons derived from Alzheimer’s patients. And once again, the drug restored normal function. Beyond plaques and tangles
The experiments add to the evidence that Alzheimer’s involves a lot more than just the appearance of plaques and tangles.“We can have these metabolic changes in our brain,” Macaulay says, “but they’re reversible.”Neurons have long been the focus of Alzheimer’s research. But the new results also show how other kinds of cells in the brain can play an important role in the disease.The brain is a bit like a beehive, where a neuron is the queen, Macaulay says. But she’s kept alive by worker bees, like astrocytes, which are asked to do more as Alzheimer’s changes the brain.“Those worker bees are getting unbelievably taxed from all the things they are being asked to do,” Macaulay says. “When that happens, then the whole system doesn’t work well.”Metabolic treatments that restore astrocytes and other helper cells in the brain could someday augment existing Alzheimer’s drugs that remove amyloid plaques, Macauley says.And the metabolic approach may be able to improve memory and thinking — something amyloid drugs don’t do.“Maybe this can make your astrocytes and your neurons work a little bit better, so that you function a little bit better,” Macaulay says.But first, she says, the promising results will have to be replicated in people.Copyright 2024 NPRTags NPR News Facebook Twitter LinkedIn Email
Prioritizing the unexpected: New brain mechanism uncovered
Researchers have discovered how two brain areas, neocortex and thalamus, work together to detect discrepancies between what animals expect from their environment and actual events. These prediction errors are implemented by selective boosting of unexpected sensory information. These findings enhance our understanding of predictive processing in the brain and could offer insights into how brain circuits are altered in autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs).
The research, published today in Nature, outlines how scientists at the Sainsbury Wellcome Centre at UCL studied mice in a virtual reality environment to take us a step closer to understanding both the nature of prediction error signals in the brain as well as the mechanisms by which they arise.
“Our brains constantly predict what to expect in the world around us and the consequences of our actions. When these predictions turn out wrong, this causes strong activation of different brain areas, and such prediction error signals are important for helping us learn from our mistakes and update our predictions. But despite their importance, surprisingly little is known about the neural circuit mechanisms responsible for their implementation in the brain,” explained Professor Sonja Hofer, Group Leader at SWC and corresponding author on the paper.
To study how the brain processes expected and unexpected events, the researchers placed mice in a virtual reality environment where they could navigate along a familiar corridor to get to a reward. The virtual environment enabled the team to precisely control visual input and introduce unexpected images on the walls. By using a technique called two-photon calcium imaging, the researchers were able to record the neural activity from many individual neurons in primary visual cortex, the first area in our neocortex to receive visual information from the eyes.
“Previous theories proposed that prediction error signals encode how the actual visual input is different from expectations, but surprisingly we found no experimental evidence for this. Instead, we discovered that the brain boosts the responses of neurons that have the strongest preference for the unexpected visual input. The error signal we observe is a consequence of this selective amplification of visual information. This implies that our brain detects discrepancies between predictions and actual inputs to make unexpected events more salient” explained Dr Shohei Furutachi, Senior Research Fellow in the Hofer and Mrsic-Flogel labs at SWC and first author on the study.
To understand how the brain generates this amplification of the unexpected sensory input in the visual cortex, the team used a technique called optogenetics to inactivate or activate different groups of neurons. They found two groups of neurons that were important for causing the prediction error signal in the visual cortex: vasoactive intestinal polypeptide (VIP)-expressing inhibitory interneurons in V1 and a thalamic brain region called the pulvinar, which integrates information from many neocortical and subcortical areas and is strongly connected to V1. But the researchers found that these two groups of neurons interact in a surprising way.
“Often in neuroscience we focus on studying one brain region or pathway at a time. But coming from a molecular biology background, I was fascinated by how different molecular pathways synergistically interact to enable flexible and contextual regulation. I decided to test the possibility that cooperation could be occurring at the level of neural circuits, between VIP neurons and the pulvinar,” explained Dr Furutachi.
And indeed, Dr Furutachi’s work revealed that VIP neurons and pulvinar act synergistically together. VIP neurons act like a switch board: when they are off, the pulvinar suppresses activity in the neocortex, but when VIP neurons are on, the pulvinar can strongly and selectively boost sensory responses in the neocortex. The cooperative interaction of these two pathways thus mediates the sensory prediction error signals in visual cortex.
The next steps for the team are to explore how and where in the brain the animals’ predictions are compared with the actual sensory input to compute sensory prediction errors and how prediction error signals drive learning. They are also exploring how their findings could help contribute to understanding ASDs and SSDs.
“It has been proposed that ASDs and SSDs both can be explained by an imbalance in the prediction error system. We are now trying to apply our discovery to ASDs and SSDs model animals to study the mechanistic neural circuit underpinnings of these disorders,” explained Dr Furutachi.
This research was funded by the Sainsbury Wellcome Centre Core Grant from the Gatsby Charity Foundation and Wellcome (219627/Z/19/Z and 090843/F/09/Z); a Wellcome Investigator Award (219561/Z/19/Z); the Gatsby Charitable Foundation (GAT3212 and GAT3361); the Wellcome Trust (090843/E/09/Z and 217211/Z/19/Z); European Research Council (HigherVision 337797; NeuroV1sion 616509); the SNSF (31003A 169525); Biozentrum core funds (University of Basel).