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Category: neuroscience – Page 523

Signaling Pathway Implicated in Inflammation and Functional Decline during Aging

Low-grade inflammation contributes to age-related decline and impairment, but the precise pathways responsible for this inflammation and their impact on natural aging have until now remained elusive.

A study headed by researchers at the Swiss Federal Institute of Technology Lausanne (EPFL) has now shown that a molecular signaling pathway known as cGAS/STING plays a critical role in driving chronic inflammation and functional decline during aging. Andrea Ablasser, PhD, and colleagues found that blocking the STING protein suppressed inflammatory responses in human senescent cells and tissues, and reduced aging-related inflammation in multiple peripheral organs and in the brain in mice.

The researchers in addition studied the effects of blocking the STING protein in aged mice. As expected by its central role in driving inflammation, inhibiting STING alleviated markers of inflammation both in the periphery and in the brain. “Notably, various aging-related immune signature genes were significantly attenuated as a result of STING inhibition,” they stated. And importantly, animals receiving STING inhibitors displayed significant enhancements in spatial and associative memory, as well as improved muscle strength and physical endurance.

“Consistently, STING inhibition by H-151, a brain permeable compound, reduced the levels of immune-related signature genes in the brains of aged mice,” the scientists pointed out. “Together, these results establish STING as an important driver of aging-associated inflammation, both in the periphery and the CNS, promoting frailty and cognitive decline.”

The study advances our understanding of aging-related inflammation and also offers potential strategies for slowing cognitive deterioration in age-associated neurodegenerative conditions. The precise elucidation of the neuroimmune crosstalk governing microglial-dependent neurotoxicity also holds promise for the future study of neurodegenerative diseases. The team concluded, “Together with previous studies in models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and frontotemporal dementia, and Nieman–Pick’s disease, our study reveals notable convergence on cGAS–STING signaling in chronic neurodegenerative conditions … Our findings establish the cGAS–STING pathway as a driver of aging-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS–STING signaling as a potential strategy to halt neurodegenerative processes during old age.”

Research discovers key cause of restricted blood flow to the brain in vascular dementia

New research on mice has shed light on how high blood pressure causes changes to arteries in the brain, a process that leads to vascular dementia. The research, led by University of Manchester scientists, funded by the British Heart Foundation and published today in the journal Proceedings of the National Academy of Sciences, [1] has uncovered a route to developing the first ever drug treatments for vascular dementia that directly target a cause of the condition.

High blood pressure is the main cause of vascular dementia, a condition characterised by poor blood flow to the brain. The reduced blood supply starves brain cells of nutrients and over time they become damaged and die. Symptoms of vascular dementia include loss of energy, lack of concentration and poor memory.

It’s normal for the brain’s arteries to narrow and widen in response to changes in blood pressure. However, consistently high blood pressure causes arteries to stay narrow and restrict the brain’s blood supply. Until now, it was not known why.

Researchers find switches that control dopamine in brain

Researchers have identified two ion channel switches that regulate the release of dopamine in the brain, a first step that might one day lead to therapeutics for a wide range of diseases and disorders that currently have few solutions.

The switches help regulate learning and motivational state in mice. Humans also have hundreds of these channels, which govern many chemical and hormonal processes that influence behavior and mood. The University of Washington School of Medicine research team hopes to identify drugs to target these channels. Those drug candidates could then be tested in clinical trials.

“The ability to precisely manipulate how dopamine-producing neurons of the brain regulate different behaviors is a major step toward developing better therapies for a range of mental illnesses,” said Larry Zweifel, professor of psychiatry & behavioral sciences at the UW School of Medicine.

Yale scientists reveal two paths to autism in the developing brain

The findings were published Aug. 10 in the journal Nature Neuroscience.

“It’s amazing that children with the same symptoms end up with two distinct forms of altered neural networks,” said Dr. Flora Vaccarino, the Harris Professor in the Child Study Center at Yale School of Medicine and co-senior author of the paper.

Two distinct neurodevelopmental abnormalities that arise just weeks after the start of brain development have been associated with the emergence of autism spectrum disorder, according to a new Yale-led study in which researchers developed brain organoids from the stem cells of boys diagnosed with the disorder.

And, researchers say, the specific abnormalities seem to be dictated by the size of the child’s brain, a finding that could help doctors and researchers to diagnosis and treat autism in the future.

Study shows promise of gene therapy for alcohol use disorder

A form of gene therapy currently used to treat Parkinson’s disease may dramatically reduce alcohol use among chronic heavy drinkers, researchers at Oregon Health & Science University and institutions across the country have found.

The study in nonhuman primates showed that implanting a specific type of molecule that induces cell growth effectively resets the brain’s dopamine reward pathway in animals predisposed to heavy drinking. The gene therapy procedure involves brain surgery, and may be useful in the most severe cases of alcohol use disorder.

Already used in clinical trials to treat Parkinson’s disease, OHSU researchers found surgical treatment dramatically reduced chronic heavy drinking.

AI models are powerful, but are they biologically plausible?

About six years ago, scientists discovered a new type of more powerful neural network model known as a transformer. These models can achieve unprecedented performance, such as by generating text from prompts with near-human-like accuracy. A transformer underlies AI systems such as ChatGPT and Bard, for example. While incredibly effective, transformers are also mysterious: Unlike with other -inspired neural network models, it hasn’t been clear how to build them using biological components.

Now, researchers from MIT, the MIT-IBM Watson AI Lab, and Harvard Medical School have produced a hypothesis that may explain how a transformer could be built using biological elements in the brain. They suggest that a biological network composed of neurons and other called astrocytes could perform the same core computation as a transformer.

Quantum Material Exhibits “Non-Local” Behavior That Mimics Brain Function

We often believe computers are more efficient than humans. After all, computers can complete a complex math equation in a moment and can also recall the name of that one actor we keep forgetting. However, human brains can process complicated layers of information quickly, accurately, and with almost no energy input: recognizing a face after only seeing it once or instantly knowing the difference between a mountain and the ocean. These simple human tasks require enormous processing and energy input from computers, and even then, with varying degrees of accuracy.

Creating brain-like computers with minimal energy requirements would revolutionize nearly every aspect of modern life. Funded by the Department of Energy, Quantum Materials for Energy Efficient Neuromorphic Computing (Q-MEEN-C) — a nationwide consortium led by the University of California San Diego — has been at the forefront of this research.

UC San Diego Assistant Professor of Physics Alex Frañó is co-director of Q-MEEN-C and thinks of the center’s work in phases. In the first phase, he worked closely with President Emeritus of University of California and Professor of Physics Robert Dynes, as well as Rutgers Professor of Engineering Shriram Ramanathan. Together, their teams were successful in finding ways to create or mimic the properties of a single brain element (such as a neuron or synapse) in a quantum material.

Older mouse brains rejuvenated by protein found in young blood

A protein involved in wound healing can improve learning and memory in ageing mice1.

Platelet factor 4 (PF4) has long been known for its role in promoting blood clotting and sealing broken blood vessels. Now, researchers are wondering whether this signalling molecule could be used to treat age-related cognitive disorders such as Alzheimer’s disease.

“The therapeutic possibilities are very exciting,” says geneticist and anti-ageing scientist David Sinclair at Harvard University in Boston, Massachusetts, who was not involved in the research. The study was published on 16 August in Nature.

Young blood, old brains.

A platelet factor joins the list of blood components that might have anti-ageing effects.

New findings show how the brain prepares to make choices during decision-making

Free will?

Neuroscientists and psychologists have been trying for decades to better understand how humans make decisions, in the hope to devise more effective interventions to promote healthy and beneficial lifestyle choices. Two brain regions that have been linked to decision-making are the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC).

Researchers at University of California, Berkeley (UC Berkeley), have been conducting extensive research focusing on these two areas of the brain and exploring their involvement in . In a recent paper published in Nature Neuroscience, they presented interesting new findings that could shed light on the through which the brain prepares to make choices.

“We previously used neural recordings to determine what was going on during decision-making,” Joni Wallis, one of the researchers who carried out the study, told Medical Xpress. “We showed that OFC neurons represent the value of the options under consideration and flip-flopping them back and forth representing the value of each option in turn, as though the OFC is weighing up the two options. This flip-flopping predicts decision making: the more flip-flopping, the more likely the subject is to make a suboptimal choice or to take a long time over their decision.”

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