MONDAY, April 24, 2023 (HealthDay News) — Reading is fundamental, but it’s also a complex skill. Now, a new study sheds more light on how the brain makes sense of the written word.
Researchers found that two key brain “networks” work in tandem to help people read sentences — so folks not only grasp the meanings of individual words but also process the bigger picture of what’s being said.
Because reading is such an essential daily activity, it’s easy to take it for granted, said study leader Oscar Woolnough , a research fellow with McGovern Medical School at UTHealth Houston.
“That is, until you lose that ability,” he said.
Woolnough pointed to the example of aphasia, which impairs people’s ability to use language — including their speech and ability to write or read. It stems from damage to the brain, often from a stroke or a head injury. People are also reading…
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If researchers can better understand how the healthy brain allows people to read, Woolnough said, that could improve understanding of aphasia and other types of reading impairment.
For the latest study, the researchers recruited patients with epilepsy who’d had electrodes implanted in their brains to try to identify the source of their seizures.
That allowed Woolnough’s team to record the participants’ brain activity as they read — precisely charting the timing of events in a way not possible with noninvasive imaging of the brain.
Researchers had the 36 participants silently read various sentences and word lists — some composed of real words and some composed of nonsense “Jabberwocky” words (based on Lewis Carroll’s ” Jabberwocky ” poem).
It turned out that when people were reading real sentences, two distinct networks in the brain’s frontotemporal cortex jumped into action. In the first one, activity progressively increased as readers absorbed sentences — a ramping up not seen when people read a word list.
That, Woolnough explained, suggests the network is adding up the combined meaning of the individual words in a sentence, and building the bigger picture of what’s being said.
The second network the researchers identified worked differently: It was more active when people were reading word lists, versus sentences. But that’s not because it was lazy during sentence reading.
As Woolnough explained it, the second network seems to become more efficient when people are reading sentences — because the context of the sentence makes it easier to process the individual words.
“Your brain can start to predict what’s coming next,” he said.
The findings — published recently in the Proceedings of the National Academy of Sciences — may not have any immediate implications for addressing reading disorders.
But experts said the study highlights the complexity of a task that is vital to everyday life.
Reading ability cannot be pinpointed to any one hub in the brain, said Monica McQuaid , director of the adult literacy program at Montefiore Medical Center’s Fisher Landau Center for the Treatment of Learning Disabilities in Bronx, N.Y.
Instead, it involves an orchestration of activity from various areas of the brain.
Dyslexia, for instance, sometimes gets misunderstood as a disorder where people see words “backwards,” McQuaid said. But the issue is not a visual one, she explained. It’s one of language processing.
So addressing dyslexia takes a “multi-sensory” approach, McQuaid explained. Instead of, say, just showing a child the word “cat,” a therapist can also use a picture of a cat, the recorded sound of a cat or integrate the movement of a cat — to “build meaning.”
When it comes to aphasia, people commonly think it’s a speech impairment, said Sarah Wallace , a professor of communication science and disorders at the University of Pittsburgh.
In reality, she said, aphasia impacts all language processing — speaking, writing and reading.Like McQuaid, Wallace pointed to the array of brain areas involved in reading, and the need for “multi-faceted” approaches to managing impairments.There are therapies to help people with aphasia improve their reading abilities, generally involving reading aloud. At the same time, Wallace said, it’s also important to make the task easier: Technology is one way to help, with text-to-speech devices that present written text and computerized speech at the same time, for example.Technology, though, has also made everyone more reliant on reading, Wallace pointed out. Emails and text messages have replaced the old-fashioned phone call.”Reading is such a huge part of our everyday lives,” Wallace said. “It’s part of how we make new relationships, and sustain relationships.”So it’s “critically important,” she said, to better understand such a fundamental human ability. More information The American Speech-Language Hearing Association has more on aphasia .SOURCES: Oscar Woolnough, PhD, postdoctoral research fellow, Department of Neurosurgery, McGovern Medical School at UTHealth Houston; Sarah Wallace, PhD, CCC-SLP, professor, communication science and disorders, School of Health & Rehabilitation Sciences, University of Pittsburgh; Monica McQuaid, PhD, director, Adult Literacy Program, Fisher Landau Center for the Treatment of Learning Disabilities, Children’s Evaluation and Rehabilitation Center at Montefiore, Bronx, N.Y.; Proceedings of the National Academy of Sciences , April 17, 2023, online 0 Comments Tags Dcc Wire Tncen Health-and-wellness Healthday Consumer News Originally published on consumer.healthday.com , part of the BLOX Digital Content Exchange .
Indigenous communities in lowland Bolivia, such as the Tsimané and Mosetén, have some of the lowest rates of heart and brain disease due to optimal levels of food consumption and exercise. New research indicates that these communities’ lifestyles, which balance daily exertion and food abundance, contribute to healthy brain aging and reduced risk of disease. Indigenous communities residing in the tropical forests of lowland Bolivia have reported some of the lowest rates of heart disease and brain disease in recorded scientific history. Now, research conducted by USC on the Tsimané and Mosetén communities indicates that a balanced combination of food consumption and physical activity can maximize healthy brain aging and decrease the likelihood of disease.
The study was recently published in the journal Proceedings of the National Academy of Sciences .
The advent of industrialization has brought about numerous benefits, including increased availability of food, reduced physical toil, and improved healthcare access. However, our current way of life has also resulted in a lack of exercise and overconsumption of food, leading to the rise of obesity. Unfortunately, this sedentary lifestyle and obesity are linked to smaller brain volumes and quicker cognitive decline.
To better understand the tipping point where abundance and ease begin to undermine health, the researchers enrolled 1,165 Tsimané and Mosetén adults, aged 40-94 years, and provided transportation for participants from their remote villages to the closest hospital with CT scanning equipment.
The Tsimané have some of the lowest rates of heart and brain disease in the world. Credit: Tsimane Health and Life History Project Team
The team used CT scans to measure brain volume by age. They also measured participants’ body mass index, blood pressure, total cholesterol, and other markers of energy and overall health.
Researchers found that the Tsimané and Mosetén experience less brain atrophy and improved cardiovascular health compared to industrialized populations in the U.S. and Europe. Rates of age-related brain atrophy, or brain shrinking, are correlated with risks of degenerative diseases like dementia and Alzheimer’s.
“The lives of our pre-industrial ancestors were punctured by limited food availability,” said Andrei Irimia, an assistant professor of gerontology, biomedical engineering, quantitative/computational biology, and neuroscience at the USC Leonard Davis School of Gerontology and co-corresponding author of the study. “Humans historically spent a lot of time exercising out of necessity to find food, and their brain aging profiles reflected this lifestyle.” The Mosetén: A bridge between pre- and post-industrialized societies
The findings also illustrated key differences between the two Indigenous societies. The Mosetén are a “sister” population to the Tsimané in that they share similar languages, ancestral history, and a subsistence lifestyle. However, the Mosetén have more exposure to modern technology, medicine, infrastructure, and education.
“The Mosetén serve as an important intermediary population that allows us to compare a wide spectrum of lifestyle and health care factors. This is more advantageous than a straight comparison between the Tsimané and the industrialized world,” Irimia said.
Irimia said that, along this continuum, the Mosetén showed better health than modern populations in Europe and North America — but not as good as that of the Tsimané.
Among the Tsimané, surprisingly, BMI and somewhat higher levels of “bad cholesterol” were associated with bigger brain volumes for age. This, however, may be due to individuals being more muscular, on average, than individuals in industrialized countries who have comparable BMIs.
Still, both the Tsimané and Mosetén come closer to the “sweet spot,” or balance between daily exertion and food abundance, that the authors think may be key to healthy brain aging. The future of preventative medicine relies on an understanding of humans’ evolutionary past
The study’s authors explained that people living in societies with abundant food and little requirement for physical activity face a conflict between what they consciously know is best for their health and the cravings, or drives, that come from our evolutionary past.
“During our evolutionary past, more food and less calories spent in getting it resulted in improved health, well-being and ultimately higher reproductive success or Darwinian fitness,” notes Hillard Kaplan, a professor of health economics and anthropology at Chapman University who has studied the Tsimané for nearly two decades. “This evolutionary history selected for psychological and physiological traits that made us desirous of extra food and less physical work, and with industrialization, those traits lead us to overshoot the mark.”
According to Irimia, the best place to be in terms of brain health and risk for disease is the “sweet spot” where the brain is being provided with neither too little nor too much food and nutrients, and where you have a vigorous amount of exercise.
“This ideal set of conditions for disease prevention prompts us to consider whether our industrialized lifestyles increase our risk of disease,” he said.
Reference: “Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations” by Hillard Kaplan, Paul L. Hooper, Margaret Gatz, Wendy J. Mack, E. Meng Law, Helena C. Chui, M. Linda Sutherland, James D. Sutherland, Christopher J. Rowan, L. Samuel Wann, Adel H. Allam, Randall C. Thompson, David E. Michalik, Guido Lombardi, Michael I. Miyamoto, Daniel Eid Rodriguez, Juan Copajira Adrian, Raul Quispe Gutierrez, Bret A. Beheim, Daniel K. Cummings, Edmond Seabright, Sarah Alami, Angela R. Garcia, Kenneth Buetow, Gregory S. Thomas, Caleb E. Finch, Jonathan Stieglitz, Benjamin C. Trumble, Michael D. Gurven and Andrei Irimia, 20 March 2023, Proceedings of the National Academy of Sciences .
The study was funded by the National Institute on Aging, the National Science Foundation, and the French National Research Agency – Investissements d’Avenir.
Hippocampal neurons (yellow) surrounded by astrocytes (green) in a cell culture from the study. Image provided by the authors. Credit: Taher Saif, Justin Rhodes, and Ki Yun Lee Physical activity is frequently cited as a means of improving physical and mental health. Researchers at the Beckman Institute for Advanced Science and Technology have shown that it may also improve brain health more directly. They studied how the chemical signals released by exercising muscles promote neuronal development in the brain.
Their work appears in the journal Neuroscience .
When muscles contract during exercise , like the biceps working to lift a heavy weight, they release a variety of compounds into the bloodstream. These compounds can travel to different parts of the body, including the brain. The researchers were particularly interested in how exercise could benefit a particular part of the brain called the hippocampus.
“The hippocampus is a crucial area for learning and memory, and therefore cognitive health,” said Ki Yun Lee, a Ph.D. student in mechanical science and engineering at the University of Illinois Urbana-Champaign and the study’s lead author. Understanding how exercise benefits the hippocampus could therefore lead to exercise-based treatments for a variety of conditions including Alzheimer’s disease.
To isolate the chemicals released by contracting muscles and test them on hippocampal neurons , the researchers collected small muscle cell samples from mice and grew them in cell culture dishes in the lab. When the muscle cells matured, they began to contract on their own, releasing their chemical signals into the cell culture.
The research team added the culture, which now contained the chemical signals from the mature muscle cells, to another culture containing hippocampal neurons and other support cells known as astrocytes . Using several measures, including immunofluorescent and calcium imaging to track cell growth and multi-electrode arrays to record neuronal electrical activity, they examined how exposure to these chemical signals affected the hippocampal cells.
The results were striking. Exposure to the chemical signals from contracting muscle cells caused hippocampal neurons to generate larger and more frequent electrical signals —a sign of robust growth and health. Within a few days, the neurons started firing these electrical signals more synchronously, suggesting that the neurons were forming a more mature network together and mimicking the organization of neurons in the brain.
However, the researchers still had questions about how these chemical signals led to growth and development of hippocampal neurons. To uncover more of the pathway linking exercise to better brain health, they next focused on the role of astrocytes in mediating this relationship.
“Astrocytes are the first responders in the brain before the compounds from muscles reach the neurons,” Lee said. Perhaps, then, they played a role in helping neurons respond to these signals.
The researchers found that removing astrocytes from the cell cultures caused the neurons to fire even more electrical signals, suggesting that without the astrocytes, the neurons continued to grow—perhaps to a point where they might become unmanageable.
“Astrocytes play a critical role in mediating the effects of exercise,” Lee said. “By regulating neuronal activity and preventing hyperexcitability of neurons, astrocytes contribute to the balance necessary for optimal brain function.”
Understanding the chemical pathway between muscle contraction and the growth and regulation of hippocampal neurons is just the first step in understanding how exercise helps improve brain health.
“Ultimately, our research may contribute to the development of more effective exercise regimens for cognitive disorders such as Alzheimer’s disease,” Lee said.
In addition to Lee, the team also included Beckman faculty members Justin Rhodes, a professor of psychology; and Taher Saif, a professor of mechanical science and engineering.
Provided by Beckman Institute for Advanced Science and Technology
( Natural News ) Walnuts, with their hard shells, are the healthiest of all nuts and should be eaten as part of a healthy diet. According to researchers from Pennsylvania, walnuts contain the highest concentration of antioxidants among known nuts.
Dr. Joe Vinson from the University of Scranton discovered that a handful of walnuts contain twice as many antioxidants as a handful of any other commonly eaten nut. This makes walnuts excellent sources of beneficial, naturally occurring chemicals that can fight oxidative stress.
Here are eight more reasons why you should eat walnuts every day. Walnuts support liver detoxification
Loaded with omega-3 fatty acids, the master antioxidant glutathione and the amino acid arginine, walnuts can cleanse your liver naturally by detoxifying ammonia. Because they help increase blood circulation, walnuts speed up the delivery of toxins to the liver, the organ that facilitates their elimination from the body.
According to a study published in the Biomedical and Pharmacology Journal , the arginine in walnuts has immune-supporting effects , especially under catabolic conditions. Arginine also helps in the treatment of liver disorders, such as liver cirrhosis and fatty liver disease. Walnuts support heart health
Walnuts are rich in nutrients that are great for your heart, such as omega-3 fatty acids, vitamin E, folate and magnesium.
The healthy omega-3 fats , more specifically alpha-linolenic acid, present in walnuts can help raise your good cholesterol levels, lower bad cholesterol and prevent the development of erratic heart rhythms. Eating walnuts regularly has been proven to help reduce inflammation in the arteries, which can prevent heart disease.
In a study published in the journal Nutrition, Metabolism & Cardiovascular Disease , researchers found that walnut eaters have a better heart disease risk profile , including a smaller waist circumference and lower body mass index, blood pressure and blood triglyceride levels, than non-walnut eaters and those who eat other nuts. Walnuts support brain health
Walnuts are known as “brain food,” but it is not only due to their brain-like shape. Walnuts are rich in healthy fatty acids, iodine and selenium that can improve brain function.
Studies have shown that walnuts can also reduce inflammation in the brain , which is linked to the development of neurodegenerative diseases like Alzheimer’s.
According to a study published in the journal Nutrients , the addition of walnuts in one’s diet helps reduce the risk of mild cognitive impairment and neurodegenerative diseases. Walnuts can keep your gut healthy
Studies suggest that if your gut is rich in health-promoting microbes, you’re more likely to have a healthy gut, a strong immune system and good overall health. Eating walnuts may be one way to support a healthy gut microflora.
A randomized controlled trial published in the journal Nutrients found that consuming 1.5 ounces (43 grams) of walnuts every day helps increase beneficial gut bacteria that butyrate, a short-chain fatty acid that nourishes your gut and promotes good gut health. Walnuts fight cancer
Test-tube, animal and human observational studies, including one published in the journal Gynecologic and Obstetric Investigation , show that walnuts are great at fighting cancer due to their antioxidant properties , which give them the ability to protect the body against breast, colon and prostate cancer.
A study published in the journal Critical Reviews in Food Science and Nutrition reported that walnuts are rich in ellagitannins, which certain gut microbes can convert to compounds called urolithins. The anti-inflammatory properties of urolithins can help lower your risk of developing colorectal cancer. Walnuts can help you lose weight
Research has found that eating a handful of walnuts every day can help stimulate fat loss and promote a healthy weight. Walnuts are known for their ability to suppress appetite , thanks to the presence of omega-3 fatty acids, plant sterols, protein and fiber that help curb hunger. (Related: Walnuts reduce hunger and cravings by changing your brain .)
A study published in the journal Diabetes, Obesity and Metabolism also found that walnut consumption increases the activation of the insula , a brain region involved in appetite and impulse control, to help curb appetite when you see “highly desirable” food. Walnuts support blood sugar control
Walnuts are diabetes-friendly nuts , being low in carbohydrates that could elevate glucose levels. On the other hand, walnuts are high in fiber, protein and healthy fats that could help prevent blood sugar spikes, says dietitian-nutritionist Cheryl Mussato, founder of Eat Well to Be Well in Osage City, Kansas. Walnuts strengthen your bones
Walnuts are a great source of copper, which can neutralize superoxide radicals produced during bone resorption. Walnuts are also rich in magnesium, which improves bone mineral density, and manganese, a co-factor for several enzymes involved in bone formation. The best way to eat walnuts
Walnuts can be eaten directly from their shell. You can soak them overnight and eat them first thing in the morning. Soaking eases digestion, lowers the level of phytic acid in walnuts and promotes metabolism and nutrient absorption.
As nutritious as walnuts are, you don’t need to eat a lot to experience their benefits. Moderate consumption of walnuts has been shown to be the best way to enjoy all the wholesome goodness this superfood has to offer. Snack on seven to 10 walnuts per day or add them to your favorite recipes to stay healthy.
Watch the following video to learn how walnuts can keep your gut healthy . Keep your gut healthy with walnuts
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Eating walnuts found to protect the colon from cancerous tumors . Walnuts are a delicious way to take care of your heart . Help manage stress, blood pressure with walnuts . Sources include: BBC.com BiomedPharmaJournal.org NMCD-jounral.com NCBI.NLM.NIH.gov PubMed.NCBI.NLM.NIH.gov 1 PubMed.NCBI.NLM.NIH.gov 2 PubMed.NCBI.NLM.NIH.gov 3 NDTV.com Wiley.com EverydayHealth.com HealthierSteps.com Brighteon.com
Credit: Pixabay/CC0 Public Domain If you ever thought your digestive system’s only role was to break down food, think again.
According to microbiome researcher Christopher Lowry, “what happens in the gut affects other parts of the body, including the brain.” And much of this activity is related to trillions of good and bad bacteria —collectively called our “microbiome”—that inhabit our gastrointestinal tract.
Lowry, who is currently conducting research at the Department of Integrative Physiology and Center for Neuroscience at the University of Colorado, Boulder on the relationship between stress-related disorders and the bacteria that live in our guts, was a featured speaker at a daylong workshop hosted by the Institute for Brain Potential in Cheyenne, Wyoming, titled “Understanding the Gut Brain.”
“Americans are microbially deprived,” said Lowry. “Gut microbes are critical for a healthy gut and a healthy brain,” and a diversity of good bugs appears to be the most beneficial.
That’s because each type of microbe has a distinct effect on the body. Some produce natural antibiotics to fight infections, for instance. Others enhance our body’s ability to extract energy from food. Still others produce chemicals that can actually improve our moods and calm stress. When the balance of these good bugs gets out of whack, we open ourselves to not-so-good conditions.
So how do we encourage the growth of beneficial bacteria in our guts? Spend more time in nature, Lowry suggested. That’s where we encounter a wide variety of healthful microbes.
And, consume a variety of foods that feed good bacteria.
Top of the list? Plants. Health-promoting microbes thrive on fibers found in foods that sprout from the ground.
“Each plant has its own microbiome,” Lowry explained. And according to results from the American Gut Project, the largest published study to date of the human microbiome, people who ate at least 30 different types of plant foods a week had more diverse bacteria in their guts than those who ate 10 or less.
My husband and I are not vegetarians, but we do consume our fair share of fruit, vegetables, beans and grains. How hard would it be to eat 30 varieties of these foods every week?
We took the challenge. For a week, I recorded every different type of plant food we ate, no matter how much or how little. For example, our salad one night had cabbage, kale, carrots, raisins and sunflower seeds. That’s five!
The next day we had blueberries and bananas in our oatmeal, three more. Celery, onion, beans, corn, tomatoes and garlic in my stew the next day added another six to our list.
It was kind of fun … and not impossible. I found myself searching for olives to toss into egg salad. And each type of nut I ate for a snack contributed to a wider diversity of my microbiome.
The point, according to this and other researchers, is that our bodies thrive on variety. And when it comes to healthful food choices, that may be a critical key to health.
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Summary: Stimulating the Supramammilary nucleus in the hypothalamus enhanced adult-born neurons in the hippocampus of mouse models of Alzheimer’s disease. These modified adult-born neurons restored both cognitive impairments and mood-related disorders associated with Alzheimer’s in the mice.
In adult human brains, the hippocampus generates new neurons (adult-born neurons, or ABNs) throughout life, helping us maintain memories and regulate emotions. Scientists call this process “adult hippocampus neurogenesis (AHN)”. In people with Alzheimer’s disease (AD), this process is impaired, leading to reduced production of ABNs with poorer qualities.
Given that AD patients often develop both cognitive symptoms (such as memory loss) and non-cognitive symptoms (such as anxiety and depression) for which AHN plays a critical role, one way to help Alzheimer’s patients achieve symptom relief could be to restore AHN.
Published in the journal Cell Stem Cell , research from UNC School of Medicine scientists demonstrated that stimulating a brain region called Supramammilary nucleus (SuM) located in the hypothalamus effectively enhanced adult-born neurons in the otherwise impaired Alzheimer’s brains of mice.
After patterned stimulation of SuM, AD brains developed more ABNs with improved qualities. Importantly, activation of these SuM-modified ABNs restored both cognitive and affective deficits in AD mouse models.
“It’s been a longstanding question whether AHN can be sufficiently enhanced in impaired AD brains to improve brain function,” said senior author Juan Song, PhD, associate professor of pharmacology and a Jeffrey Houpt Distinguished Investigator at the UNC School of Medicine.
“An important point to consider when addressing these questions is the low-level hippocampal neurogenesis, which becomes even lower in AD patients.
By manipulating a small number of ABNs in the AD brain, we demonstrate that ABNs can be enhanced even in the presence of AD pathology, and these enhanced ABNs are important for the restoration of behaviors and hippocampal function.”
To enhance ABNs in AD brains, Song and colleagues adopted an elegant two-step ABN-enhancing strategy by first stimulating SuM using a patterned optogenetic paradigm with the goal of promoting the generation and developmental properties of ABNs, followed by stimulating the activity of SuM-enhanced ABNs using chemogenetics.
Optogenetics involves the use of light to alter the activity of brain cells expressing light-sensitive opsin genes. Chemogenetics involves the use of inert molecules to alter the activity of brain cells expressing designer’s receptors.
“Interestingly, SuM stimulation alone or activation of ABNs without SuM stimulation failed to restore behavioral deficits in AD mice.” Song said. “These results suggest that multi-level enhancement of ABNs — namely increasing their number, improving their developmental properties, and enhancing their activity — is required to achieve their therapeutic benefits in AD brains.” Supramammilary nucleus projections to the hippocampus (yellow), adult-born new neurons (purple), microglia (magenta), and plaques (lavender) in the Alzheimer’s mouse brain. Credit: Song Lab, UNC School of Medicine When Song and colleagues further analyzed the protein changes in the hippocampus of AD mice in response to activation of SuM-enhanced ABNs, the researchers found that several well-known protein pathways were activated inside cells.
These pathways include the ones important for synaptic plasticity of neuronal cells that allow enhanced communication among them, as well as the ones important for phagocytosis of non-neuronal microglia that allow efficient plaque clearance.
“It is striking that multi-level enhancement of ABNs through combined SuM and ABN stimulations allows such a small number of ABNs make profound functional contribution in diseased AD brains,” Song said.
“We are eager to find out the mechanisms underlying these beneficial effects mediated by activation of SuM-enhanced ABNs on AD pathology and hippocampal function. Future efforts will be needed to develop drugs that mimic these beneficial effects mediated by activation of SuM-enhanced ABNs. Ultimately, the hope is to develop first-in-class, highly targeted therapies to treat AD and related dementia.”
Funding: The National Institutes of Health funded this research through grants R01MH111773, R01MH122692, RF1AG058160, R01NS104530 to Juan Song and R21AG071229, R01GM133107 to co-author Xian Chen, PhD, professor of biochemistry and biophysics at the UNC School of Medicine. About this Alzheimer’s disease research news
Author: Mark Derewicz
Contact: Mark Derewicz – UNC
Image: The image is credited to Song Lab, UNC School of Medicine
Original Research: Open access.
“ Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease ” by Juan Song et al. Cell Stem Cell
Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease Highlights
Patterned optogenetic stimulation of SuM enhances hippocampal neurogenesis in AD
Activation of SuM-enhanced ABNs rescues memory and emotion deficits in AD
Activation of SuM-enhanced ABNs promotes hippocampal plasticity and activity in AD
Activation of SuM-enhanced ABNs increases microglia phagocytosis of plaques in AD Summary Patients with Alzheimer’s disease (AD) exhibit progressive memory loss, depression, and anxiety, accompanied by impaired adult hippocampal neurogenesis (AHN). Whether AHN can be enhanced in impaired AD brain to restore cognitive and affective function remains elusive.Here, we report that patterned optogenetic stimulation of the hypothalamic supramammillary nucleus (SuM) enhances AHN in two distinct AD mouse models, 5×FAD and 3×Tg-AD. Strikingly, the chemogenetic activation of SuM-enhanced adult-born neurons (ABNs) rescues memory and emotion deficits in these AD mice. By contrast, SuM stimulation alone or activation of ABNs without SuM modification fails to restore behavioral deficits.Furthermore, quantitative phosphoproteomics analyses reveal activation of the canonical pathways related to synaptic plasticity and microglia phagocytosis of plaques following acute chemogenetic activation of SuM-enhanced (vs. control) ABNs.Our study establishes the activity-dependent contribution of SuM-enhanced ABNs in modulating AD-related deficits and informs signaling mechanisms mediated by the activation of SuM-enhanced ABNs.Join our Newsletter I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )Sign up to receive our recent neuroscience headlines and summaries sent to your email once a day, totally free.