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Comment by Dr. Krishna Kumari Challa on August 16, 2024 at 9:08am

Sleep resets neurons for new memories the next day, study finds

While everyone knows that a good night's sleep restores energy, a new  study finds it resets another vital function: memory.

Learning or experiencing new things activates neurons in the hippocampus, a region of the brain vital for memory. Later, while we sleep, those same neurons repeat the same pattern of activity, which is how the brain consolidates those memories that are then stored in a large area called the cortex. But how is it that we can keep learning new things for a lifetime without using up all of our neurons?

A study, "A Hippocampal Circuit Mechanism to Balance Memory Reactivation During Sleep,"  published in Science, finds at certain times during deep sleep, certain parts of the hippocampus go silent, allowing those neurons to reset.

This mechanism could allow the brain to reuse the same resources, the same neurons, for new learning the next day.

The hippocampus is divided into three regions: CA1, CA2 and CA3. CA1 and CA3 are involved in encoding memories related to time and space and are well-studied; less is known about CA2, which the current study found generates this silencing and resetting of the hippocampus during sleep.

The researchers now realized that there are other hippocampal states that happen during sleep where everything is silenced. The CA1 and CA3 regions that had been very active were suddenly quiet. It's a reset of memory, and this state is generated by the middle region, CA2.

Cells called pyramidal neurons are thought to be the active neurons that matter for functional purposes, such as learning. Another type of cell, called interneurons, has different subtypes. The researchers discovered that the brain has parallel circuits regulated by these two types of interneurons—one that regulates memory, the other that allows for resetting of memories.

The researchers think they now have the tools to boost memory, by tinkering with the mechanisms of memory consolidation, which could be applied when memory function falters, such as in Alzheimer's disease. Importantly, they also have evidence for exploring ways to erase negative or traumatic memories, which may then help treat conditions such as post-traumatic stress disorder.

The result helps explain why all animals require sleep, not only to fix memories, but also to reset the brain and keep it working during waking hours. 

 Lindsay A. Karaba et al, A hippocampal circuit mechanism to balance memory reactivation during sleep, Science (2024). DOI: 10.1126/science.ado5708. www.science.org/doi/10.1126/science.ado5708

Comment by Dr. Krishna Kumari Challa on August 16, 2024 at 8:59am

The new study focuses on the MEC, but not on the stored information needed for spatial navigation or an animal's current location. Instead, the experiments performed now concentrate on how this brain region creates maps of future positions, which are continuously updated as animals move.

While rats traversed an open square field in search of freely available water that was moved around to different locations, the researchers recorded all movements, which included hundreds of trajectories. At the same time, they recorded the activity of individual brain cells in the MEC.

Afterward, they checked how well the  brain activity over time matched the rats' changing positions.

They found that the activity of some brain cells in the MEC created an internal grid that mapped future positions within the field. For example, an MEC cell might encode a certain location in the field, but only when a rat reached a spot 30 cm to 40 cm earlier in a route that eventually crossed that location—regardless of which direction the rat was coming from.

This is very different from the grid cells that helped win the Nobel Prize, which become active only when an animal is currently in a particular location. The authors call the newly discovered neurons "predictive grid cells," and conducted several follow-up experiments to get a better idea of what exactly they encode.

First, they tested whether the newly discovered grid cells predicted the future location in terms of distance or time from the present. They found that both were encoded, although the "gridness" of the cells was higher when considering distance.

They also found that future positions were faithfully encoded in different situations, whether the rats were trying to go to specific targets or if they were randomly foraging for food. This means that the function of the predictive grid cells is not limited to goal-directed behavior.

This study provides important insights into the mechanisms of spatial navigation and episodic memory formation in hippocampal and entorhinal cortical circuits.

Ayako Ouchi et al, Predictive grid coding in the medial entorhinal cortex, Science (2024). DOI: 10.1126/science.ado4166. www.science.org/doi/10.1126/science.ado4166

Comment by Dr. Krishna Kumari Challa on August 16, 2024 at 8:54am

Navigating the future: Brain cells that plan where to go

Researchers  have discovered a region of the brain that encodes where an animal is planning to be in the near future. Linked to internal maps of spatial locations and past movements, activity in the newly discovered grid cells accurately predicts future locations as an animal travels around its environment.

Published in Science on August 15, the study helps explain how planned spatial navigation is possible.

It might seem effortless, but navigating the world requires quite a bit of under-the-hood brain activity. For example, simply walking around a supermarket picking up groceries requires internalized maps of the outside world, information about one's own changing position and speed, and memories about where one has been and what one is trying to buy.

Much of this kind of information is contained in cells within two connected parts of the brain—the hippocampus and the medial entorhinal cortex, or MEC for short—which are extremely similar in all mammals, from rats to humans. In particular, the MEC contains maps of an animal's current location in space, a discovery that won the Nobel Prize for Physiology or Medicine in 2014.

Prediction grid cells in the medial entorhinal cortex became active before rats entered the region of space that they encode. In this video, activity of two neurons is represented by the flashing of red and blue squares. for convenience, the squares are placed in the location of the grid that the neurons encode. Credit: RIKEN

Part 1

Comment by Dr. Krishna Kumari Challa on August 16, 2024 at 8:31am

Cleaning up the aging brain: Scientists restore brain's waste removal system

Alzheimer's, Parkinson's, and other neurological disorders can be seen as "dirty brain" diseases, where the brain struggles to clear out harmful waste. Aging is a key risk factor because, as we grow older, our brain's ability to remove toxic buildup slows down. However, new research in mice demonstrates that it's possible to reverse age-related effects and restore the brain's waste-clearing process.

This research work shows that restoring cervical lymph vessel function can substantially rescue the slower removal of waste from the brain associated with age. Moreover, this was accomplished with a drug already being used clinically, offering a potential treatment strategy.

First described by Nedergaard and her colleagues in 2012, the glymphatic system is the brain's unique waste removal process that uses cerebrospinal fluid (CSF) to wash away excess proteins generated by energy hungry neurons and other cells in the brain during normal activity. This discovery pointed the way for potential new approaches to treat diseases commonly associated with the accumulation of protein waste in the brain, such as Alzheimer's (beta amyloid and tau) and Parkinson's (alpha-synuclein).

In healthy and young brains, the glymphatic system does a good job of flushing away these toxic proteins. However, as we age, this system slows, setting the stage for these diseases.

Once laden with protein waste, CSF in the skull needs to make its way to the lymphatic system and ultimately the kidneys, where it is processed along with the body's other waste. The new research combines advanced imaging and particle tracking techniques to describe for the first time in detail the route via the cervical lymph vessels in the neck through which half of dirty CSF exits the brain.

In addition to measuring the flow of CSF, the researchers were able to observe and record the pulsing of lymph vessels in the neck that helps draw CSF out of the brain.

Unlike the cardiovascular system which has one big pump, the heart, fluid in the lymphatic system is instead transported by a network of tiny pumps. These microscopic pumps, called lymphangions, have valves to prevent backflow and are strung together, one after another, to form lymph vessels.

The researchers found that as the mice aged, the frequency of contractions decreased, and the valves failed. As a result, the speed of dirty CSF flowing out of the brains of older mice was 63 percent slower compared to younger animals.

The team then set out to see if they could revive the lymphangions and identified a drug called prostaglandin F2α, a hormone-like compound commonly used medically to induce labor and known to aid smooth muscle contraction. The lymphangions are lined with smooth muscle cells, and when the researchers applied the drug to the cervical lymph vessels in older mice, the frequency of contractions and the flow of dirty CSF from the brain both increased, returning to a level of efficiency found in younger mice.

These vessels are conveniently located near the surface of the skin, scientists know they are important, and they now know how to accelerate function. They can see how this approach, perhaps combined with other interventions, could be the basis for future therapies for these diseases.

Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage, Nature Aging (2024). DOI: 10.1038/s43587-024-00691-3

Comment by Dr. Krishna Kumari Challa on August 16, 2024 at 8:19am

By mapping out the evolving roles of various cell types involved in regeneration, Mokalled and her colleagues found that the flexibility of the surviving injured neurons and their capacity to immediately reprogram after injury lead the chain of events that are required for spinal cord regeneration.

If these injury-surviving neurons are disabled, zebrafish do not regain their normal swim capacity, even though regenerative stem cells remain present.

When the long wiring of the spinal cord is crushed or severed in people and other mammals, it sets off a chain of toxicity events that kills the neurons and makes the spinal cord environment hostile against repair mechanisms.

This neuronal toxicity could provide some explanation for the failure of attempts to harness stem cells to treat spinal cord injuries in people. Rather than focus on regeneration with stem cells, the new study suggests that any successful method to heal spinal cord injuries in people must start with saving the injured neurons from death.

Neurons by themselves, without connections to other cells, do not survive.

In zebrafish, researchers think severed neurons can overcome the stress of injury because their flexibility helps them establish new local connections immediately after injury. This research work suggests this is a temporary mechanism that buys time, protecting neurons from death and allowing the system to preserve neuronal circuitry while building and regenerating the main spinal cord.

There is some evidence that this capacity is present but dormant in mammalian neurons, so this may be a route to new therapies, according to the researchers.

They  are hopeful that identifying the genes that orchestrate this protective process in zebrafish—versions of which also are present in the human genome —will help us find ways to protect neurons in people from the waves of cell death that we see following spinal cord injuries.

Zebrafish use surprising strategy to regrow spinal cord, Nature Communications (2024). DOI: 10.1038/s41467-024-50628-y

Part 2

Comment by Dr. Krishna Kumari Challa on August 16, 2024 at 8:16am

Zebrafish use surprising strategy to regrow spinal cord: Findings could help identify ways to heal spinal cord damage

Zebrafish are members of a rarefied group of vertebrates capable of fully healing a severed spinal cord. A clear understanding of how this regeneration takes place could provide clues toward strategies for healing spinal cord injuries in people. Such injuries can be devastating, causing permanent loss of sensation and movement.

A new study maps out a detailed atlas of all the cells involved—and how they work together—in regenerating the zebrafish spinal cord.

In an unexpected finding, the researchers showed that survival and adaptability of the severed neurons themselves is required for full spinal cord regeneration. Surprisingly, the study showed that stem cells capable of forming new neurons—and typically thought of as central to regeneration—play a complementary role but don't lead the process.

Unlike humans' and other mammals' spinal cord injuries, in which damaged neurons always die, the damaged neurons of zebrafish dramatically alter their cellular functions in response to injury, first to survive and then to take on new and central roles in orchestrating the precise events that govern healing, the researchers found. Scientists knew that zebrafish neurons survive spinal cord injury, and this new study reveals how they do it.

The surprising observation the researchers made is that there are strong neuronal protection and repair mechanisms happening right after injury. They think these protective mechanisms allow neurons to survive the injury and then adopt a kind of spontaneous plasticity—or flexibility in their functions—that gives the fish time to regenerate new neurons to achieve full recovery.

This study has identified genetic targets that will help researchers promote this type of plasticity in the cells of people and other mammals.

Part 1

Comment by Dr. Krishna Kumari Challa on August 15, 2024 at 11:04am

WHO declares mpox outbreaks in Africa a global health emergency as a new form of the virus spreads

The World Health Organization declared the mpox outbreaks in Congo and elsewhere in Africa a global emergency on Wednesday, with cases confirmed among children and adults in more than a dozen countries and a new form of the virus spreading. Few vaccine doses are available on the continent.

Earlier this week, the Africa Centers for Disease Control and Prevention announced that the mpox outbreaks were a public health emergency, with more than 500 deaths, and called for international help to stop the virus' spread.

The Africa CDC previously said mpox, also known as monkeypox, has been detected in 13 countries this year, and more than 96% of all cases and deaths are in Congo. Cases are up 160% and deaths are up 19% compared with the same period last year. So far, there have been more than 14,000 cases and 524 people have died.

Source: various news agencies

Comment by Dr. Krishna Kumari Challa on August 15, 2024 at 11:01am

Chemicals in makeup, sunscreen may raise odds for dangerous pregnancy complication

Chemicals commonly found in sunscreen, makeup and other personal care products could be putting pregnancies at risk, a new study warns.

Phenols and parabens in these products increase a pregnant woman's risk of high blood pressure by 57%, particularly at 24 to 28 weeks of gestation, researchers reported Aug. 14 in the journal Environmental Health Perspectives.

Researchers found chemicals in everyday soaps, lotions, makeup, sunscreen and other personal care products and consumer products [that] increased risk of hypertension.

Phenols and parabens are used as UV filters in sunscreens, and to prevent the growth of harmful mold and bacteria in makeup and cosmetics, researchers said.

Parabens alone are used in about 80% of personal care products, the research team said in background notes.

Phenols' and parabens' link to hypertension in pregnancy is troubling. High blood pressure during pregnancy reduces blood flow to the placenta, so the fetus might wind up starved of oxygen and nutrients. As a result, the fetus might suffer from restricted growth, low birth weight and premature birth, the researchers explained.

It's dangerous for expecting moms as well, increasing their risk of complications like preeclampsia and stroke.

Both mother and child also have an increased likelihood that they will suffer from high blood pressure, diabetes and heart disease long after pregnancy.

There are several reasons why the chemicals might be increasing blood pressure in pregnant women, the researchers said.

Phenols and parabens are known to increase inflammation and oxidative stress in humans, which has been linked to high blood pressure, researchers noted.

The chemicals also are known to disrupt hormones in humans, and these hormones also play a role in regulating blood pressure, they added.

ulia R. Varshavsky et al, Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort, Environmental Health Perspectives (2024). DOI: 10.1289/EHP14008

Comment by Dr. Krishna Kumari Challa on August 15, 2024 at 10:55am

Early life exposure to common chemical permanently disrupts gut microbiome, mouse study finds

Early life exposure to 'forever chemicals' in the environment permanently disrupts the gut microbiome in mice, contributing to the development of metabolic disease in later life, according to new research.

The results, published Aug. 14 in the journal Environmental Health Perspectives, suggest that human exposure to these chemicals during early childhood may be contributing to the recent epidemic of metabolic disorders, including obesity and type 2 diabetes among adults.

The researchers focused specifically on 2,3,7,8-tetrachlorodibenzofuran (TCDF), a widespread persistent organic pollutant (POP) that is a byproduct of waste incineration, metal production, and fossil-fuel and wood combustion.

TCDF accumulates in the food chain, and humans are primarily exposed through consumption of high-fat foods, such as meat, dairy products and some fish. Babies can be exposed through consumption of breast milk.

POPs are pervasive in the environment and nearly every living organism has been exposed

The negative health effects of these chemicals are well documented and include birth defects and cancer. This study is the first to suggest that early-life exposure to a certain POP, called TCDF, also disrupts the gut microbiome and is associated with metabolic disorders later in life.

Yuan Tian et al, Effects of Early Life Exposures to the Aryl Hydrocarbon Receptor Ligand TCDF on Gut Microbiota and Host Metabolic Homeostasis in C57BL/6J Mice, Environmental Health Perspectives (2024). DOI: 10.1289/EHP13356

Comment by Dr. Krishna Kumari Challa on August 15, 2024 at 10:38am

Scientists discover method to activate dormant stem cells in the brain

Scientists have discovered a novel pathway to wake up dormant neural stem cells, offering potential new therapies for neurodevelopmental disorders such as autism, learning disabilities, and cerebral palsy.

In the mammalian adult brain, most neural stem cells, which originate from the nervous system and can grow into various types of brain cells, stay dormant until they receive specific signals that activate them. Once woken up, they produce new neurons, aiding in brain repair and growth.

Defects in neural stem cell activation are associated with aging-related cognitive decline and neurodevelopmental disorders such as microcephaly, a condition where a baby's head is much smaller than expected because its brain has not developed properly.

Neurodevelopmental disorders affect around five percent of children and adolescents worldwide and lead to impaired cognition, communication, adaptive behavior and psychomotor skills.

To study this activation, the scientists turned to Drosophila or fruit flies. Similar to mammals, the neural stem cells of fruit flies stay dormant till they are awakened. Their findings, published in Science Advances, showed that a type of glial cell named astrocytes—traditionally thought to provide structural and nutritional support—are important for waking up dormant neural stem cells in the brains of fruit flies.

Using super-resolution microscopy with 10-times magnifying power, the team of scientists examined the tiny fiber structures that are a hallmark of dormant neural stem cells of fruit flies.

These fine structures, around 1.5 µm in diameter (or 20 times smaller than the diameter of a human hair), are protrusions extending from the cell body, and are rich in actin or protein filaments. A specific type of Formin protein can activate these filaments and cause them to assemble.

Kun-Yang Lin et al, Astrocytes control quiescent NSC reactivation via GPCR signaling–mediated F-actin remodeling, Science Advances (2024). DOI: 10.1126/sciadv.adl4694

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