Category Archives: Neuroscience

Neuroscience

Breathing Is The Key to Memory Consolidation During Sleep – Neuroscience News

Summary: Researchers unveiled a critical link between breathing and memory consolidation during sleep. In an extensive study involving EEG and breathing analysis, they discovered that specific sleep-related brain rhythms are directly influenced by our breathing patterns.

These findings highlight the importance of respiration in reinforcing learned information while we sleep. This work could have significant implications for addressing age-related memory issues and sleep disorders.

Key Facts:

Source: LMU

How are memories consolidated during sleep?

In 2021, researchers led by Dr. Thomas Schreiner, leader of the Emmy Noether junior research group at LMUs Department of Psychology, had already shown there was a direct relationship between the emergence of certain sleep-related brain activity patterns and the reactivation of memory contents during sleep.

However, it was still unclear whether these rhythms are orchestrated by a central pacemaker. So the researchers joined up with scientists from the Max Planck Institute for Human Development in Berlin and the University of Oxford to reanalyze the data. Their results have identified respiration as a potential pacemaker.

That is to say, our breathing influences how memories are consolidated during sleep, says Schreiner.

Learning processes investigated in sleep laboratory

For their original study, the researchers showed 20 study participants 120 images over the course of two sessions. All the pictures were associated with certain words. Then the participants slept for around two hours in the sleep laboratory.

When they awoke, they were questioned about the associations they had learned. During the entire learning and sleep period, their brain activity was recorded by means of EEG, along with their breathing.

The researchers discovered that previously learned contents were spontaneously reactivated by the sleeping brain during the presence of so-called slow oscillations and sleep spindles (short phases of increased brain activity).

The precision of the coupling of these sleep-related brain rhythms increases from childhood to adolescenceand then declines again during aging, says Schreiner.

Breathing and brain activity are linked

Because respiration frequency also changes with age, the researchers then analyzed the data in relation to the recorded breathing and were able to establish a connection between them.

Our results show that our breathing and the emergence of characteristic slow oscillation and spindle patterns are linked, says Schreiner.

Although other studies had already established a connection between breathing and cognition during wake, our work makes clear that respiration is also important for memory processing during sleep.

Older people often suffer from sleep disorders, respiratory disorders, and declining memory function. Schreiner plans to further investigate whether there are connections between these phenomena and whether interventions such as the use of CPAP masks, which are already used to treat sleep apnea make sense from a cognitive perspective.

Author: Constanze Drewlo Source: LMU Contact: Constanze Drewlo LMU Image: The image is credited to Neuroscience News

Original Research: Open access. Respiration modulates sleep oscillations and memory reactivation in humans by Thomas Schreiner et al. Nature Communications

Abstract

Respiration modulates sleep oscillations and memory reactivation in humans

The beneficial effect of sleep on memory consolidation relies on the precise interplay of slow oscillations and spindles. However, whether these rhythms are orchestrated by an underlying pacemaker has remained elusive.

Here, we tested the relationship between respiration, which has been shown to impact brain rhythms and cognition during wake, sleep-related oscillations and memory reactivation in humans.

We re-analysed an existing dataset, where scalp electroencephalography and respiration were recorded throughout an experiment in which participants (N=20) acquired associative memories before taking a nap.

Our results reveal that respiration modulates the emergence of sleep oscillations. Specifically, slow oscillations, spindles as well as their interplay (i.e., slow-oscillation_spindle complexes) systematically increase towards inhalation peaks.

Moreover, the strength of respiration slow-oscillation_spindle coupling is linked to the extent of memory reactivation (i.e., classifier evidence in favour of the previously learned stimulus category) during slow-oscillation_spindles.

Our results identify a clear association between respiration and memory consolidation in humans and highlight the role of brain-body interactions during sleep.

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Breathing Is The Key to Memory Consolidation During Sleep - Neuroscience News

Neuroscience

DeepSouth: A Revolutionary Supercomputer for Simulating the Human Brain | 2024 Launch – Medriva

In an ambitious leap forward in computational neuroscience, a supercomputer designed to simulate the entire human brain is set to become operational in 2024. This cutting-edge development, named DeepSouth, holds the potential to revolutionize our understanding of the human brain and advance the field of neuroscience.

Set to switch on in 2024, DeepSouth is the worlds first supercomputer capable of simulating networks at the scale of the human brain. Using a neuromorphic system that mimics biological processes, it can perform a staggering 228 trillion synaptic operations per second. This system is purpose-built to operate like networks of neurons, demanding less power and facilitating greater efficiencies. The supercomputer is a collaboration between Western Sydney University, the University of Sydney, the University of Melbourne, and the University of Aachen in Germany.

This unprecedented development is expected to lead to significant advances in smart devices, sensors, and AI applications. But perhaps the most profound impact of DeepSouth will be its contribution to our understanding of the healthy and diseased human brain. By replicating the brains neural network and cognitive functions, the supercomputer paves the way for groundbreaking insights into brain disorders and neurological conditions.

DeepSouth is not the only attempt at creating a biological computer. Researchers worldwide are exploring the possibility of building computers powered by actual brain cells. Such advancements could potentially create a cyborg brain vastly more powerful than our own. The hope is to better understand how brains can use such little power to process vast amounts of information.

DeepSouth is part of a larger initiative known as the Human Brain Project. This multinational collaboration aims to simulate the entire human brain by 2024. The goal is to delve deeper into the brains functions and develop new treatments for brain-related diseases. This ambitious project has garnered significant attention from the scientific community and offers a promising direction for future research.

In conclusion, the advent of a supercomputer capable of simulating the entire human brain signals a new era in neuroscience and AI research. As we await the operational launch of DeepSouth in 2024, the scientific community and the world at large watch with bated breath, eager to witness the revolutionary insights this development will bring to our understanding of the most complex organ in the human body. The future of neuroscience holds exciting possibilities and is poised for unparalleled growth and discovery.

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DeepSouth: A Revolutionary Supercomputer for Simulating the Human Brain | 2024 Launch - Medriva

Neuroscience

Protein Key to Neuroprotection and Aging Discovered – Neuroscience News

Summary: Researchers made a pivotal discovery in neuroprotection. They identified how Elovanoid-34, a molecule in the brain, modulates the protein TXNRD1 to combat oxidative stress, a precursor to neurodegenerative diseases.

This breakthrough reveals that Elovanoid-34 can prevent cell death in conditions like Age-Related Macular Degeneration by regulating oxidative stress.

The study emphasizes the potential of this discovery for developing new therapies for age-related diseases and promoting successful nervous system aging.

Key Facts:

Source: LSU

Scientists at LSU Health New Orleans Neuroscience Center of Excellence, led by Nicolas Bazan, MD, PhD, Boyd Professor and Director, have identified a new mechanism that regulates a protein key for cell survival.

It appears to protect against the excessive oxidative stress that precedes the development of neurodegenerative diseases of the brain and eye.

Results are published in the Nature journal,Cell Death & Disease.

This discovery goes beyond the commonly studied transcriptional modulation, suggesting its impact on protection against oxidative stress-related diseases and extension of lifespan, notes Dr. Bazan, who is also the Ernest C. and Ivette C. Villere Chair for Retinal Degenerations and Bollinger Family Professor in Alzheimers Disease.

We found that Elovanoid-34 modulates the activity of the protein, TXNRD1, which is central to the initiation cascade of oxidative stress.

Elovanoid-34 is part of a class of molecules in the brain discovered by the Bazan lab that synchronize cell-to-cell communication and neuroinflammation-immune activity in response to injury or disease.

Elovanoids are bioactive chemical messengers made from omega-3 very long-chain polyunsaturated fatty acids. They are released on demand when cells are damaged or stressed.

Oxidative stress occurs when there is an imbalance between free radicals and antioxidant defenses to detoxify them. It can lead to cell and tissue damage and the onset of diseases.

The research team, which included scientists from the Swiss company Biognosys AG, identified the proteins affected by Elavamoid-34. Using proteomics, they screened 130,000 protein sequences corresponding to 4,749 proteins and discovered that only one changed in structure upon contact with Elovanoid-34.

Researchers found that TXNRD1 is a crucial component of the antioxidant system, Glutathione, and targets a regulator of Ferroptosis, a type of cell death. This is particularly the case in Age-Related Macular Degeneration where the support cells of the photoreceptors of the light in the retina succumb to excessive oxidative stress conditions.

These cells, called retinal pigment epithelial (RPE) cells, can be rescued from death by Elovanoid-34, stopping the neurodegeneration of the retina and blindness. The current study uses human RPE cells, which were developed in the Bazan lab.

This breakthrough discovery opens new therapeutic avenues for various pathologies and the promotion of successful aging of the nervous system, concludes Dr. Bazan.

LSU Health New Orleans Neuroscience Center co-authors also included Drs. Jorgelina Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, and Pranab K. Mukherjee. Co-authors from Biognosys AG included Yuehan Feng, Jakob Vowinckel and Tobias Treiber.

The research was supported by a grant from the National Eye Institute of the National Institutes of Health and the Eye, Ear, Nose & Throat Foundation in New Orleans.

The present discovery opens a new dimension to understanding the complex multifactorial process of aging, adds Dr. Bazan.

The gradual decline of functions in aging does engage excessive oxidative stress further magnified by co-morbidities such asdiabetes and cardiovascular disorders. In fact, a clear connection is revealed by the present discovery because elovanoidsalso target neuronal cell senescence and epigenetic signaling.

Overall, the protein discovered now to be a site of brain and retina (and likely other organs) protection by elovanoids opens avenues of targeted therapeutics for age-related diseases, stroke, ALS and traumatic brain injury, as well as to sustain healthy, successful aging.

Author: Leslie Capo Source: LSU Contact: Leslie Capo LSU Image: The image is credited to Neuroscience News

Original Research: Open access. Elovanoid-N34 modulates TXNRD1 key in protection against oxidative stress-related diseases by Nicolas Bazan. Cell Death and Disease

Abstract

Elovanoid-N34 modulates TXNRD1 key in protection against oxidative stress-related diseases

The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases.

Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival.

Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3.

This lipid mediator induces TXNRD1 structure changes that modify the FAD interface domain, leading to its activity modulation. The addition of ELV-N34 decreased membrane and cytosolic TXNRD1 activity, suggesting localizations for the targeted reductase.

These results show for the first time that the lipid mediator ELV-N34 directly modulates TXNRD1 activity, underling its protection in several pathologies when uncompensated oxidative stress (UOS) evolves.

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Protein Key to Neuroprotection and Aging Discovered - Neuroscience News

Neuroscience

Revolutionizing Understanding of The Human Brain – DeepSouth Project – Medriva

Revolutionizing Understanding of The Human Brain

In an unprecedented technological development, a supercomputer capable of simulating the complexities of the human brain is set to be operational by 2024. This groundbreaking project, known as DeepSouth, aims to replicate the human brains structure and function, offering valuable insights into cognitive neuroscience, brain-inspired computing, and brain disorders.

DeepSouth, the worlds first supercomputer to simulate the entire human brain, has been designed to perform an astounding 228 trillion synaptic operations per second. This rate closely rivals the estimated operational speed of the human brain. Developed by Western Sydney University, the supercomputer leverages a neuromorphic system to efficiently emulate large networks of spiking neurons.

The DeepSouth project aims to offer an in-depth understanding of how our brains process vast amounts of information while using minimal power. By mimicking the brains operations, researchers hope to gain a better understanding of its intricacies and design more efficient AI systems. This breakthrough development could revolutionize our understanding of how our brains work and pave the way for the creation of a cyborg brain significantly more potent than our own.

DeepSouths operational launch is highly anticipated within the neuroscience and AI research community. The supercomputer is expected to significantly impact medical research, potentially leading to advancements in understanding brain disorders and developing new treatments. The insights derived from this supercomputer could also revolutionize brain-inspired computing, opening new frontiers in artificial intelligence.

The Human Brain Project, a collaborative endeavor involving scientists and researchers from various disciplines, is at the center of this technological feat. The supercomputer will be used to create a virtual model of the human brain, a resource that could be invaluable to both neuroscience and AI researchers. The project is a testament to the power of multi-disciplinary collaboration, combining expertise from different fields to push the boundaries of what is possible in neuroscience and technology.

As we approach 2024, the world eagerly awaits the unveiling of DeepSouth. This supercomputer promises not only to shed light on the enigmatic human brain but also to inspire new engineering solutions within the AI space. The potential of this technology is immense, and its impact on neuroscience, AI, and beyond is yet to be fully realized. As technology continues to advance at a rapid pace, projects like DeepSouth remind us of the incredible potential that lies at the intersection of neuroscience and artificial intelligence.

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Revolutionizing Understanding of The Human Brain - DeepSouth Project - Medriva

Neuroscience

Gene Clusters Reveal Brain Link to Anxiety Disorders – Neuroscience News

Summary: Researchers made a significant breakthrough in understanding the genetic basis of anxiety disorders (ADs), which affect over 280 million people globally.

By analyzing the spatiotemporal transcriptomic data of AD-associated genes in human brains, they identified two distinct gene clusters with specific expression patterns in the cerebral nuclei, midbrain, and limbic system, areas previously linked to AD behaviors. These clusters correspond to glutamatergic and serotonergic/dopaminergic signaling, respectively, and their distinct expression during various developmental stages suggests a role in the development of AD symptoms.

This research provides crucial insights into the genetic and neurophysiological underpinnings of ADs and their subtypes, opening pathways for targeted treatments.

Key Facts:

Source: ASHBI

Anxiety disorders (ADs) affect more than 280 million people worldwide, making them one of the most common mental health conditions. ADs have a genetic basis as seen from inheritance in families, and people with one subtype of AD tend to have another subtype, suggesting a shared genetic basis. Although the brain circuitry involved in ADs has been identified, its link with gene expression remains unclear.

Two researchers at Kyoto University in Japan set out to uncover this link and found two gene clusters expressed in the brain.

In previous research, targeted gene sequencing and genome-wide association studies (GWAS) have revealed frequently occurring mutations in people with AD or anxiety-associated personality traits. These mutations have been mapped to specific genes in the human genome.

Meanwhile, neuroimaging techniques such as functional MRI (fMRI) and PET scans have shown that activity in specific neural circuits can predict anxious temperament in rhesus macaques, and micro-stimulation techniques in these monkeys can demonstrate which neural circuits are involved in the AD symptoms.

The Kyoto University researchers, Ms. Karunakaran andDr. Amemori, investigated whether AD-associated genes are expressed in the same neural circuits identified by the imaging and micro-stimulation techniques.

Specifically, they examined whether the regions where AD-associated genes are expressed could reveal the neurocircuitry of AD by analyzing the spatiotemporal transcriptomic data of more than 200 genes linked to four AD subtypes, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and panic disorder, in over 200 brain regions of normal human brains available inthe Allen Brain Atlas.

Using statistical tests, the researchers found that AD-associated genes are highly expressed in the cerebral nuclei, the midbrain, and the limbic system.

Further analysis of these areas by hierarchical clustering showed two AD gene clusters with distinct spatial expression profilesone highly expressed in the limbic system and a specific set of cerebral nuclei and the other in the midbrain and a different set of cerebral nuclei; previous physiological research had suggested that these brain structures are involved in regulating AD behaviors.

Additional analyses revealed that the two clusters were indeed linked to different behaviors. The two clusters also showed distinct enrichment patterns for subtype-specific genes, establishing a clear link between each cluster and specific AD subtypes.

One cluster was involved in glutamatergic receptor signaling, while the other was associated with serotonergic and dopaminergic signaling, further supporting a dichotomy in the neurophysiology of ADs. Additionally, the two clusters were linked to distinct region-specific gene networks and cell types.

Finally, the researchers examined developmental transcriptome data to track the expression patterns of the AD genes during brain development and found that the two spatial clusters have distinct and negatively correlated identities at specific developmental stages.

One cluster is highly expressed during late infancy and adulthood, while the other is expressed during the late prenatal stage and early childhood. Thus, mutations in AD-associated genes might disrupt the normal timing of their expression, potentially impacting the development of signaling pathways and neural circuits, thereby producing the symptoms associated with AD.

In this research, the scientists discovered two gene clusters associated with AD that have distinct spatial and temporal expression patterns and functional profiles within the human brain. Further investigation of these gene clusters might provide new insights into the underlying causes of AD.

Author: Hiromi Nakao-Inoue Source: ASHBI Contact: Hiromi Nakao-Inoue ASHBI Image: The image is credited to Neuroscience News

Original Research: Open access. Spatiotemporal expression patterns of anxiety disorder-associated genes by Kalyani B. Karunakaran&Ken-ichi Amemori. Translational Psychiatry

Abstract

Spatiotemporal expression patterns of anxiety disorder-associated genes

Anxiety disorders (ADs) are the most common form of mental disorder that affects millions of individuals worldwide. Although physiological studies have revealed the neural circuits related to AD symptoms, how AD-associated genes are spatiotemporally expressed in the human brain still remains unclear.

In this study, we integrated genome-wide association studies of four human AD subtypesgeneralized anxiety disorder, social anxiety disorder, panic disorder, and obsessive-compulsive disorderwith spatial gene expression patterns.

Our investigation uncovered a novel division among AD-associated genes, marked by significant and distinct expression enrichments in the cerebral nuclei, limbic, and midbrain regions.

Each gene cluster was associated with specific anxiety-related behaviors, signaling pathways, region-specific gene networks, and cell types. Notably, we observed a significant negative correlation in the temporal expression patterns of these gene clusters during various developmental stages.

Moreover, the specific brain regions enriched in each gene group aligned with neural circuits previously associated with negative decision-making and anxious temperament. These results suggest that the two distinct gene clusters may underlie separate neural systems involved in anxiety.

As a result, our findings bridge the gap between genes and neural circuitry, shedding light on the mechanisms underlying AD-associated behaviors.

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Gene Clusters Reveal Brain Link to Anxiety Disorders - Neuroscience News

Neuroscience

KBR, HJF Partner on Critical Neuroscience Research to Support Military Personnel; Byron Bright Quoted – ExecutiveBiz

KBR will join with The Henry M. Jackson Foundation on theService Personnel Advancing Research in Chronic Traumatic Encephalopathy contract.

The SPARC contract supports neuroscience research for service members and will specifically focus on patients affected by traumatic brain injuries, KBR said Monday.

According to Byron Bright, president of government solutions for the U.S. at KBR, the program will help ensure the well-being of service members.

Supporting our military is one of KBRs top priorities, and I am pleased to witness the growth of our human health and technology portfolio to further this important work, said Bright, a Wash100 awardee.

The research teams from KBR and HJF willcollaborate withthe Uniformed Services University and the University of California San Francisco.Under the terms of the SPARC contract, KBR will provide outreach, education and data analytics to support critical neuroscience research for the prevention and treatment of military members with chronic traumatic encephalopathy.

This cost-plus-fixed-fee contract could reach 52 months and includes assisting in developing therapeutics to treat the CTE illness. The SPARC program leverages the experience and knowledge from established programs to further the understanding, treatment and, ultimately, prevention of CTE in military personnel.

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KBR, HJF Partner on Critical Neuroscience Research to Support Military Personnel; Byron Bright Quoted - ExecutiveBiz

Neuroscience

Unveiling the Dark Genome: LINE-1’s Role in Disease – Neuroscience News

Summary: A new study illuminated a part of the dark genome, specifically focusing on LINE-1, a genetic element linked to various diseases and aging.

Researchers have provided the first high-resolution images and structural details of LINE-1, an ancient genetic parasite with about 100 active copies in each person. This research, involving international collaboration, reveals LINE-1s mechanism of integrating DNA into the human genome and its correlation with diseases like cancer and neurodegeneration.

The studys findings offer a foundation for potential treatments targeting this retrotransposon.

Key Facts:

Source: University of Alberta

Research published today inNaturesheds light on a small part of the so-called dark genome the 98 percent of the human genome whose biological function is largely not known.

In the study, an international multidisciplinary team reported thefirst high-resolution images and structural detailsof a genetic element known as LINE-1, which inserts itself into the human genome and is implicated in diseases such as cancer, autoimmune disorders and neurodegeneration, and even aging. The work provides a target for potential new treatments moving forward.

LINE-1 is described as an ancient genetic parasite with about 100 potentially active copies in each person. LINE-1 activity is often correlated with disease. Unlike DNA, which makes RNA and then proteins, retrotransposons like LINE-1 work backwards, making DNA from RNA and then inserting it into the genome.

Retrotransposons are often referred to as jumping genes that insert themselves into our chromosomes with a copy-and-paste mechanism, explainsMatthias Gtte, professor and chair of the Department of Medical Microbiology and Immunology at the University of Alberta and one of the eight co-corresponding authors.

For this paper, we discovered the essential steps in this process, which could then lead us to ways to inhibit the enzyme and eventually treat those diseases.

The team included researchers from institutions in the United States and Europe, as well as biotechnology partners. Gttes lab was the only Canadian contributor to the research, which was led by investigators from Harvard Medical School and biotechnology companyROME Therapeutics.

The researchers say their analyses reveal the inner workings of the molecular machine that has written nearly half of the human genome, and that understanding LINE-1 structure and function is important both in evolution and, increasingly, in human disease.

The Gtte lab, including research associateEgor Tchesnokov, provided much of the biochemical data in the paper.

It was a large team effort with world-class structural biologists, says Gtte. Effective treatments for important human diseases can only be developed with a very strong scientific foundation.

Author: Ross Neitz Source: University of Alberta Contact: Ross Neitz University of Alberta Image: The image is credited to Neuroscience News

Original Research: Closed access. Structures, functions, and adaptations of the human LINE-1 ORF2 protein by Matthias Gtte et al. Nature

Abstract

Structures, functions, and adaptations of the human LINE-1 ORF2 protein

The LINE-1 (L1) retrotransposon is an ancient genetic parasite that has written around one third of the human genome through a copy-and-paste mechanism catalyzed by its multifunctional enzyme, open reading frame 2 protein (ORF2p).

ORF2p reverse transcriptase (RT) and endonuclease activities have been implicated in the pathophysiology of cancer, autoimmunity, and aging, making ORF2p a potential therapeutic target. However, a lack of structural and mechanistic knowledge has hampered efforts to rationally exploit it.

We report structures of the human ORF2p core (residues 238-1061, including the RT domain) by X-ray crystallography and cryo-EM in multiple conformational states. Our analyses reveal two novel folded domains, extensive contacts to RNA templates, and associated adaptations that contribute to unique aspects of the L1 replication cycle. Computed integrative structural models of full-length ORF2p show a dynamic closed ring conformation that appears to open during retrotransposition.

We characterize ORF2p RT inhibition and reveal its underlying structural basis. Imaging and biochemistry reveal that non-canonical cytosolic ORF2p RT activity can produce RNA:DNA hybrids, activating innate immune signaling via cGAS/STING and resulting in interferon production.

In contrast to retroviral RTs, L1 RT is efficiently primed by short RNAs and hairpins, which likely explains cytosolic priming. Additional biochemical activities including processivity, DNA-directed polymerization, non-templated base addition, and template switching together allow us to propose an updated L1 insertion model.

Finally, our evolutionary analysis reveals structural conservation between ORF2p and other RNA- and DNA-dependent polymerases. We therefore provide key mechanistic insights into L1 polymerization and insertion, shed light on L1 evolutionary history, and enable rational drug development targeting L1.

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Unveiling the Dark Genome: LINE-1's Role in Disease - Neuroscience News

Neuroscience

Alzheimers discovery reveals dire effect of – EurekAlert

image:

George Bloom, PhD, researches Alzheimer's disease at the University of Virginia.

Credit: Dan Addison | University Communications

University of Virginia Alzheimers researchers have discovered how harmful tau proteins damage the essential operating instructions for our brain cells, a finding which could lead to new treatments.

The toxic protein, the researchers found, warps the shape of the nuclei of nerve cells, or neurons. This alters the function of genes contained inside and reprograms the cells to make more tau.

While the protein has long been a prime suspect in Alzheimers and other neurodegenerative tauopathies, the new research from UVAs George Bloom, Ph.D.; his recently graduated student Xuehan Sun, Ph.D.; and collaborators is among the first to identify concrete physical harms that tau causes to neurons. As such, it offers researchers exciting leads as they work to develop new treatments for Alzheimers disease and tauopathies, which are now untreatable.

A lot of fantastic research has been done by other labs to learn how toxic tau spreads from neuron to neuron in the brain, but very little is known about exactly how this toxic tau damages neurons, and that question is the motivation for our new paper, said Bloom, of UVAs Departments of Biology, Cell Biology andNeuroscience, as well as the UVA Brain Institute, the Virginia Alzheimers Disease Center and UVAs Program in Fundamental Neuroscience. The toxic tau described here is actually released from neurons, so if we can figure out how to intercept it when its floating around in the brain outside of neurons, using antibodies or other drugs, it might be possible to slow or halt progression of Alzheimers disease and other tauopathies.

Tauopathies are characterized by the buildup of tau inside the brain. Alzheimers disease is well known, but there are many other tauopathies, including frontotemporal lobar degeneration, progressive supranuclear palsy and chronic traumatic encephalopathy. These diseases typically present as dementia, personality changes and/or movement problems. There are no treatments available for non-Alzheimers tauopathies, so the UVA researchers were eager to better understand what is happening, so that scientists can find ways to prevent or treat it.

Bloom and his team discovered that tau oligomers assemblages of multiple tau proteins can have dramatic effects on the normally smooth shape of neuronal nuclei. The oligomers cause the nuclei to fold in on themselves, or invaginate, disrupting the genetic material contained within. The physical location and arrangement of genes affects how they work, so this unnatural rearrangement can have dire effects.

Our discovery that tau oligomers alter the shape of the nucleus drove us to the next step testing the idea that changes in gene expression are caused by the nuclear shape change, Bloom said. Thats exactly what we saw for many genes, and the biggest change is that the gene for tau itself increases its expression almost three-fold. So bad tau might cause more bad tau to be made by neurons that would be like a snowball rolling downhill.

The researchers found that patients with Alzheimers disease had twice as many invaginated nuclei as people without the condition. Increases were also seen in lab mice used as models of Alzheimers and another tauopathy.

The researchers say that additional research into how this process happens could open the door to new ways to prevent and treat Alzheimers and other tauopathies.

The researchers have published their findings in the scientific journal Alzheimers & Dementia. The article is open access, meaning it is free to read. The research team consisted of Xuehan Sun, Guillermo Eastman, Yu Shi, Subhi Saibaba, Ana K. Oliveira, John R. Lukens, Andrs Norambuena, Joseph A. Thompson, Michael D. Purdy, Kelly Dryden, Evelyn Pardo, James W. Mandell and Bloom. The researchers have no financial interest in the work.

The research was supported by the National Institutes of Health, grant RF1 AG051085; the Owens Family Foundation; the Cure Alzheimers Fund; Rick Sharp Alzheimers Foundation; Webb and Tate Wilson; and the NanoString nCounter Grant Program.

To keep up with the latest medical research news from UVA, subscribe to theMaking of Medicineblog.

Alzheimer s & Dementia

9-Dec-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Alzheimers discovery reveals dire effect of - EurekAlert

Neuroscience

Active Aging: Exercise and Social Life Shield Brain Health – Neuroscience News

Summary: Researchers uncovered the protective effects of physical and social activities on brain health in older adults.

Analyzing data from a 12-year longitudinal study, researchers focused on the entorhinal cortex, vital for learning and memory and vulnerable in Alzheimers disease. They found that increased physical and social activity slowed the thinning of the entorhinal cortex and, consequently, memory decline over seven years.

This research underscores the importance of an active lifestyle in preserving brain health and cognitive function in old age.

Key Facts:

Source: University of Zurich

Physical exercise is associated with a variety of positive health aspects. Numerous studies have shown that regular physical activity has a preventive effect on cardiovascular diseases, diabetes, cancer, high blood pressure and obesity.

But how do various leisure activities physical, social and cognitive affect brain health in old age?

A team of researchers from the University Research Priority Program Dynamics of Healthy Aging and from the Healthy Longevity Center of the University of Zurich (UZH) decided to investigate this question.

To this end, they examined data from a comprehensive longitudinal study on brain development and behavior in old age. The longitudinal study was set in motion 12 years ago by Lutz Jncke, meanwhile professor emeritus at UZH, who continues to supervise the project together with co-lead Susan Mrillat.

The aim of the current research was to investigate the relationships between the thickness of the entorhinal cortex, memory performance and leisure activities in cognitively healthy adults over the age of 65, for a period of seven years.

Exercise and social activity slow down neurodegeneration

The entorhinal cortex, approximately 3.5 millimeters thick, is part of the cerebral cortex in the inner part of the temporal lobe and plays a key role in learning and memory. It is also one of the brain regions that is affected early on in the development of Alzheimers disease.

Our findings show that in people who were more physically and socially active at the beginning of the study, the thickness of their entorhinal cortex decreased less over the seven-year period, says neuropsychologist Jncke.

The researchers also found that the thickness of the entorhinal cortex is closely linked to memory performance. The less the thickness of this brain structure decreased over the course of the study, the less memory performance was reduced.

Physical exercise and an active social life with friends and family are therefore important for brain health and can prevent neurodegeneration in later life, says Jncke.

Brain can be trained like a muscle

It was also shown that higher memory performance at the beginning of the study was associated with a lower decline in memory performance over the course of the study.

These findings support the idea that we have a cognitive reserve, and that the brain can be trained throughout our lives like a muscle to counteract age-related decline, says Isabel Hotz, one of the two first authors alongside Pascal Deschwanden.

In other words, it pays to be physically, mentally and socially active throughout our lives, including in later life.

Fortunately, many older people in Switzerland already seem to be living by this credo: according to the Swiss Health Survey conducted by the Swiss Federal Statistical Office in 2022, around three quarters of people over 65 get the recommended amount of physical exercise in their daily lives.

Author: Kurt Bodenmueller Source: University of Zurich Contact: Kurt Bodenmueller University of Zurich Image: The image is credited to Neuroscience News

Original Research: Open access. Associations between white matter hyperintensities, lacunes, entorhinal cortex thickness, declarative memory and leisure activity in cognitively healthy older adults: A 7-year study by Lutz Jncke et al. NeuroImage

Abstract

Associations between white matter hyperintensities, lacunes, entorhinal cortex thickness, declarative memory and leisure activity in cognitively healthy older adults: A 7-year study

Cerebral small vessel disease (cSVD) is a growing epidemic that affects brain health and cognition. Therefore, a more profound understanding of the interplay between cSVD, brain atrophy, and cognition in healthy aging is of great importance.

In this study, we examined the association between white matter hyperintensities (WMH) volume, number of lacunes, entorhinal cortex (EC) thickness, and declarative memory in cognitively healthy older adults over a seven-year period, controlling for possible confounding factors.

Because there is no cure for cSVD to date, the neuroprotective potential of an active lifestyle has been suggested. Supporting evidence, however, is scarce. Therefore, a second objective of this study is to examine the relationship between leisure activities, cSVD, EC thickness, and declarative memory.

We used a longitudinal dataset, which consisted of five measurement time points of structural MRI and psychometric cognitive ability and survey data, collected from a sample of healthy older adults (baselineN=231, age range: 6487 years, ageM=70.8 years), to investigate associations between cSVD MRI markers, EC thickness and verbal and figural memory performance.

Further, we computed physical, social, and cognitive leisure activity scores from survey-based assessments and examined their associations with brain structure and declarative memory. To provide more accurate estimates of the trajectories and cross-domain correlations, we applied latent growth curve models controlling for potential confounders.

Less age-related thinning of the right (=0.92,p<.05) and left EC (=0.82,p<.05) was related to less declarative memory decline; and a thicker EC at baseline predicted less declarative memory loss (=0.54,p<.05). Higher baseline levels of physical (=0.24,p<.05), and social leisure activity (=0.27,p<.01) predicted less thinning of right EC. No relation was found between WMH or lacunes and declarative memory or between leisure activity and declarative memory.

Higher education was initially related to more physical activity (=0.16,p<.05) and better declarative memory (=0.23,p<.001), which, however, declined steeper in participants with higher education (=.35,p<.05). Obese participants were less physically (=.18,p<.01) and socially active (=.13,p<.05) and had thinner left EC (=.14,p<.05) at baseline.

Antihypertensive medication use (=.26,p<.05), and light-to-moderate alcohol consumption (=.40,p<.001) were associated with a smaller increase in the number of lacunes whereas a larger increase in the number of lacunes was observed in current smokers (=0.30,p<.05).

Our results suggest complex relationships between cSVD MRI markers (total WMH, number of lacunes, right and left EC thickness), declarative memory, and confounding factors such as antihypertensive medication, obesity, and leisure activity.

Thus, leisure activities and having good cognitive reserve counteracting this neurodegeneration. Several confounding factors seem to contribute to the extent or progression/decline of cSVD, which needs further investigation in the future.

Since there is still no cure for cSVD, modifiable confounding factors should be studied more intensively in the future to maintain or promote brain health and thus cognitive abilities in older adults.

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Active Aging: Exercise and Social Life Shield Brain Health - Neuroscience News