AI Links Brain Rhythms to Physical “Wiring” Across Lifespan

 What is your competent? doctors' EXACT PROTOCOL TO ENSURE YOUR WHITE MATTER WIRING AND MYELIN IS WORKING PROPERLY?

Nothing, like usual!

demyelinating (24 posts to May 2012)

demyelination (12 posts to November 2021)

AI Links Brain Rhythms to Physical “Wiring” Across Lifespan

Summary: For the first time, a multinational research team has mapped how the brain’s electrical activity evolves from age 5 to 100 by linking it directly to the brain’s physical “wiring diagram.” The study introduces Xi–αNET, a generative model that explains how nerve-signal speed and anatomical connections create the patterns seen on an EEG.

By analyzing the HarMNqEEG dataset—recordings from 1,965 people across nine countries—researchers discovered that the slowing of brain waves in old age isn’t random; it is a direct reflection of declining myelin (the insulation on nerve fibers). This breakthrough suggests that simple EEG tests could become a “speedometer” for brain health, flagging neurodegenerative diseases like Parkinson’s before traditional symptoms appear.

Key Facts

• The Xi–αNET Model: This new framework treats the brain’s “background noise” ($\xi$) and rhythmic alpha waves ($\alpha$) as independent processes driven by physical signal-conduction speeds.
• The U-Shaped Journey: Nerve-signal delays follow a U-shaped curve over a lifetime—they are short in youth, stable in midlife, and lengthen significantly in old age as white matter integrity declines.
• Myelin as the “Pace Setter”: The study proved that the frequency of alpha waves is set by the thickness of myelin insulation. Heavier myelination equals faster conduction and higher-frequency brain waves.
• Clinical “Red Flags”: The model successfully detected the signature “slowing” of alpha rhythms in patients with Parkinson’s disease, proving its potential as a diagnostic tool.

Source: Science China Press

How does the human brain’s electrical activity grow from childhood, peak in adulthood, and decline in older age?

A multinational team has tackled this question by linking the brain’s “wiring diagram” and signal‑conduction speed to two familiar features of an electroencephalogram (EEG): the broadband background activity (ξ, pronounced “xi”) and the more rhythmic alpha waves.

The Xi–αNET model demonstrates that brain rhythms are reflections of the brain’s physical wiring and the efficiency of its signal highways. Credit: Neuroscience News

Their work, published in National Science Review, introduces a new model called Xi–αNET (“Xi–AlphaNET”) that explains how anatomical connections and nerve‑signal delays give rise to these patterns and how they change over the lifespan.

At the heart of the study is the HarMNqEEG dataset, a unique collection of resting‑state EEG recordings from 1,965 people aged five to 100 years. Participants were scanned in nine countries using 12 different EEG systems, and the data were harmonized to allow meaningful comparisons. Such breadth allowed the researchers to probe how the brain’s rhythms develop across an entire century of life.

Traditional analyses treat alpha waves and the background ξ signal as statistical patterns divorced from brain structure. Xi–αNET instead treats the aperiodic background (ξ) and the α‑rhythm as independent processes generated by the brain’s network.

The model uses a myelination map derived from MRI to create a hierarchy of brain regions, then estimates how signals flow through this hierarchy. It shows that across the lifespan the broadband activity is localized in frontal regions and dominated by feedforward connections (from sensory areas upward), while the α‑rhythm is strongest in posterior sensory and sensorimotor regions and dominated by feedback connections (top‑down influences).

This distinction echoes previous theories linking slower rhythms to long‑range feedback and faster rhythms to feedforward processing.

Xi–αNET also incorporates information about how long it takes for activity in one cortical region to reach another. These conduction delays are not measured directly by EEG; rather, they come from intracranial cortico‑cortical evoked responses, which provide priors on the time it takes for signals to travel between regions.

The model then estimates a subject‑specific overall delay to align these prior delays to each individual. When the team examined how these delays vary with age, they found a U‑shaped trajectory—shorter delays in youth, stable midlife values, and longer delays in older age.

Comparing this trajectory with independent MRI‑derived maps of myelination revealed that the curves closely match. In other words, the degree of insulation around nerve fibers (myelin) appears to set the pace of brain rhythms: faster conduction, reflecting heavier myelination, corresponds to higher alpha frequencies.

The strong inverse relationship—peak alpha frequency declines as conduction delays lengthen—suggests that slowing alpha waves may be an accessible marker of declining white‑matter integrity in aging or disease.

Beyond its scientific insights, the work demonstrates the power of generative models—mathematical frameworks that explicitly link structure to function. The authors show that Xi–αNET produces reliable estimates of cortical activity, effective connectivity and subject‑specific conduction delays from routine EEG recordings.

Such tools could pave the way for normative reference charts, against which individual deviations might flag developmental disorders, neurodegenerative diseases, or the effects of interventions. Preliminary analyses in the paper show that the model can detect the slowing of alpha rhythms in Parkinson’s disease, hinting at future clinical applications.

This study paints a new picture of brain rhythms: they are not free‑floating oscillations but reflections of the brain’s physical wiring and the efficiency of its signal highways. As lead author Ronaldo Garcia Reyes puts it, “By weaving together structural connections, conduction speed and electrical rhythms, we can start to understand how the brain’s architecture shapes its dynamics and why these dynamics change with age.”

Key Questions Answered:

Q: Why do our brain waves slow down as we get older?

A: It’s a matter of “insulation.” Your nerves are wrapped in myelin, which acts like the rubber coating on an electrical wire. As we age, this insulation thins out. The Xi–αNET model shows that when this “coating” degrades, the signals take longer to travel, which physically forces your brain’s alpha waves to slow down.

Q: Can an EEG now tell me my “brain age”?

A: Potentially, yes! Because the study mapped the “normal” signal speeds for every age from 5 to 100, doctors can now compare your EEG against a global “normative chart.” If your signal delays are much longer than average for your age, it could be an early warning sign of a condition like Parkinson’s or dementia.

Q: What is the difference between “background noise” and “alpha waves” in the brain?

A: Think of the background noise as the baseline hum of the brain’s sensory “uploading” (feedforward) process, mostly active in the front of the head. Alpha waves are the rhythmic “feedback” signals (top-down) that help us focus and process sensory info, mostly active in the back of the head.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this AI and neuroscience research news

Author: Bei Yan
Source: Science China Press
Contact: Bei Yan – Science China Press
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Lifespan Development of EEG Alpha and Aperiodic Component Sources is Shaped by the Connectome and Axonal Delays” by Ronaldo Garcia Reyes, Ariosky Areces Gonzalez, Ying Wang, Yu Jin, Shahwar Yasir, Maria Luisa Bringas-Vega, Mitchell Valdes-Sosa, Cheng Luo, Peng Xu, Viktor Jirsa, Dezhong Yao, Ludovico Minati, and Pedro A. Valdes-Sosa. National Science Review
DOI:10.1093/nsr/nwag076

Dopamine Links Social Isolation to Brain Myelin Damage

 You already have myelin damage from your stroke, don't let your doctor make it worse by not getting you 100% recovered and the social isolation that produces.Your competent? doctor has known of the myelin problem post stroke and already created protocols to fix that, right? Oh no, you DON'T have a functioning stroke doctor, do you? RUN AWAY!

• myelin (79 posts to April 2011)
• myelin regeneration (3 posts to August 2024)
• myelin repair (5 posts to January 2025)

Dopamine Links Social Isolation to Brain Myelin Damage

Summary: A new five-year study explores how dopamine may drive changes in brain myelin during social isolation. Researchers will track how dopamine interacts with oligodendrocytes, the cells responsible for producing myelin and supporting neuron function.

The project aims to uncover whether dopamine regulates myelin plasticity, potentially linking isolation, addiction, schizophrenia, and other conditions. The findings could open doors to treatments for disorders involving myelin breakdown, from neuropsychiatric disease to neurodegeneration.

Key Facts

• Novel Hypothesis: Dopamine may regulate myelin plasticity via oligodendrocytes.
• Isolation Impact: Social isolation alters dopamine levels and myelin structure.
• Wider Relevance: Insights may apply to conditions like addiction, MS, and schizophrenia.

Source: CUNY

Scientists know that social isolation can alter brain structure and lead to the breakdown of myelin, the fatty coating that insulates nerve fibers in the brain. But they don’t yet know exactly how or why it happens.

A new, five-year study, supported by the National Science Foundation, investigates the potential mechanisms that drive the process.

“We’re looking at the role of dopamine in regulating changes in myelin caused by social isolation,” said study leader Leora Yetnikoff, a professor of Biology and a member of the CUNY Neuroscience Collaborative at the CUNY Graduate Center, and a professor of psychology at the College of Staten Island.

Yetnikoff was recently awarded a $1 million NSF CAREER award to examine how dopamine affects  oligodendrocytes, the specialized cells in the brain and spinal cord that make myelin.

Using advanced genetic and imaging tools, her team will observe how dopamine interacts with these cells and whether changing dopamine levels can reverse the effects of social isolation on myelin.

“Traditionally, myelin is believed to be an insulator of axons,” Yetnikoff said, referring to the long and slender nerve fibers that carry messages from neuron to neuron using electricity. The myelin coats axons much like insulation on a wire, paving the way for these electrical signals to travel faster for better communication.

However, newer research focuses on oligodendrocytes as metabolic supporters, supplying the molecules to help power electrical signals traveling through axons in the brain. And without this support, axons can weaken or degenerate, the professor said.

“So, the question people are starting to ask is, ‘What other functions are these cells playing besides producing myelin?” Yetnikoff said.

The project will focus on three areas.

“One is a novel role for dopamine, which is viewed as a key neurotransmitter involved in synaptic plasticity,” she said, referring to the brain’s ability to strengthen or weaken the connections between neurons and how the brain changes with experience — making learning, memory, and adaptation possible.

“The work that we’re doing suggests — and we haven’t proven it yet — that dopamine may be communicating with the oligodendrocytes to make myelin plastic, and that’s a novel form of plasticity in the brain.”

The second looks at the broader implications of dopamine’s effect on myelin in the brain.

“Social isolation is only one phenomenon that causes changes in myelin plasticity,” said Yetnikoff, pointing to brain injury and  neuropsychiatric conditions such as schizophrenia and addiction.

“Dopamine is involved in all these conditions. Right now, we’re just looking at social isolation, but the implications are that it could potentially be involved in many other conditions.”

The third area relates to social isolation and the external factors that cause it.

“So, we’ve just come out of the COVID pandemic,” said the professor, “and there’s social isolation among the elderly. It can occur in youth, when they lock themselves up with video games and computers. So, how is that affecting the brain and what are the mechanisms involved?”

Since the 1960s, animal studies have shown that social isolation can result in altered levels of dopamine, the neurochemical most linked to motivation and pleasure. Yet, scientists are only beginning to piece together the connections between dopamine and myelin plasticity.

Yetnikoff points to a seminal study, which tracked more than 100 children in Romanian orphanages. The researchers found that neglect and psychosocial deprivation led to abnormal brain development in the orphans, especially in the prefrontal cortex, responsible for higher-level cognitive function and impulse control. 

“That work showed that myelination in their prefrontal cortex, as well as other myelinated tracts, was decreased compared to non-neglected orphans,” she said.

If her study can identify the mechanisms involved in demyelination that occurs with social isolation, she said, there’s potential to gain critical insights on other conditions seen with the deterioration of myelin — drug addiction, multiple sclerosis, Parkinson’s Disease, and other neuropsychiatric diseases among them.

Student researchers will train in the Yetnikoff Laboratory, using cutting-edge technology over the five-year-life of the project. Yetnikoff credits her students for doing much of the work that went into the proposal that won the NSF grant. “None of this would’ve happened without them,” she said.

Funding: Yetnikoff received a young investigator grant from the Brain and Behavior Research Foundation for her work on dopamine and adolescence in 2017, and a SCORE Award from the National Institutes of Health for her research on glial cells in 2021. She was granted the CUNY Feliks Gross award for outstanding research in 2022.

About this neuroscience and social isolation research news

Author: Shawn Rhea
Source: CUNY
Contact: Shawn Rhea – CUNY
Image: The image is credited to Neuroscience News

Stem Cell Grafts Show Promise in Repairing Myelin in MS

 EXACTLY how much damage to myelin did your stroke cause? How come your incompetent? doctor doesn't know that and has nothing to repair it?

• myelin (78 posts to April 2011)
• myelin regeneration (3 posts to August 2024)
• myelin repair (2 posts to January 2025)

Stem Cell Grafts Show Promise in Repairing Myelin in MS

Summary: A new study reveals that neural stem cell grafts can generate new myelin in the central nervous system, offering hope for treating progressive multiple sclerosis (MS). Researchers showed that induced neural stem cells matured into myelin-producing oligodendrocytes and safely integrated into damaged regions in a mouse model.

The findings suggest stem cell therapies could address the underlying neurodegeneration in progressive MS, beyond simply managing symptoms. This breakthrough supports the RESTORE consortium’s mission to develop patient-centered clinical trials for stem cell-based MS therapies.

Key Facts:

• New Myelin Formation: Neural stem cell grafts formed myelin-producing cells in damaged regions.
• Safe Transplants: Human induced neural stem cell grafts were shown to be safe in animal models.
• RESTORE Initiative: Findings advance efforts toward clinical trials targeting progressive MS.

Source: University of Cambridge

A study led by Cambridge researchers has shed light on how neural stem cell grafts could help restore myelin in the central nervous system.

The findings suggest that neural stem cell-based therapies hold promise as a potential treatment for chronic demyelinating disorders, particularly progressive multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease where the body’s immune system mistakenly attacks the central nervous system, leading to the destruction of myelin, the protective sheath surrounding nerve fibres. This damage is a leading cause of neurological disability in young adults.

The goal of this research is to see how these therapies may mitigate brain atrophy and slow the progression of MS.Credit: Neuroscience News

In the early stages of MS, certain cells possess the capacity to partially repair this damage by generating new myelin. However, this regenerative ability reduces significantly in the later, chronic progressive stage of the disease. This decline in repair contributes to further damage to neurons and increasing disability in individuals with progressive MS.

Despite advancements in treatments, current therapies mostly focus on managing symptoms but do not halt or reverse the damage and neurodegeneration caused. This shows the critical need for a more profound understanding of how MS progresses and to explore how stem cell technologies could help MS treatment.

The study, published in the journal Brain, was spearheaded by University of Cambridge scientist Dr. Luca Peruzzotti-Jametti and offers crucial insights into the potential of neural stem cell transplantation in pwPMS (progressive multiple sclerosis). While neural stem cell transplants present a promising avenue for repairing the damaged central nervous system, the limits of their capacity to repair are being investigated by researchers.

This study focused on using induced neural stem cells (iNSCs) in a mouse model to evaluate their ability to promote remyelination. The research showed, for the first time, that induced neural stem cells grafts can mature into oligodendrocytes, the cells responsible for producing myelin.

More importantly, the study provided evidence supporting the safety of human induced neural stem cell transplantation.

“This research provides critical evidence that induced neural stem cell grafts can effectively turn into myelin-producing cells within the damaged central nervous system, suggesting a potential new way to treat progressive MS,” said Dr. Peruzzotti-Jametti, Department of Clinical Neurosciences, University of Cambridge, the study’s first author.

The research team is investigating the underlying mechanisms of MS in the central nervous system and exploring how neural stem cell-based treatments can influence neuroprotective and anti-inflammatory processes. The goal of this research is to see how these therapies may mitigate brain atrophy and slow the progression of MS.

“Our findings represent a significant step forward in understanding how stem cell therapies can be harnessed to combat chronic demyelinating disorders,” said Stefano Pluchino, Clinical Professor of Regenerative Neuroimmunology at the Department of Clinical Neurosciences, the study’s senior author.

“We are particularly excited about the potential to develop central nervous system directed therapies that not only manage symptoms but also address the underlying neurodegenerative processes in progressive MS.

“We’ve shown we can make new myelin with stem cells, and demonstrated it is possible to target lesions with grafts. This is a major step forward in the research towards directed therapies for chronic demyelinating disorders such as progressive multiple sclerosis.”

Future research and RESTORE

This compelling evidence demonstrating the ability of neural stem cell grafts to generate new myelin in vivo within laboratory animals exhibiting MS-like lesions carries significant implications for ongoing research and the development of clinical trials.

One group dedicated to developing innovative stem cell therapies for people with progressive MS is RESTORE, a collaborative European and US consortium which includes a number of leading scientists from Cambridge University including Prof. Pluchino & Dr. Peruzzotti-Jametti. Supported by the International Progressive MS Alliance – Experimental Medicine Development Award Scheme 2025, RESTORE’s mission is to pioneer a groundbreaking efficacy clinical trial using neural stem cell-based therapy for progressive MS.  

A core focus of the group’s approach is placing patients at the heart of research, actively involving and engaging people with MS to ensure that the work addresses their needs, values, and perspectives.

The success of this study will help support the RESTORE consortium in their goal of pursuing therapies for the benefit of patients with progressive MS, and shows that neural stem cell transplantation can lead to meaningful remyelination and improved neurological outcomes in patients.

It is hoped this can potentially pave the way for more effective clinical trial designs and ultimately, a fully biological disease-modifying therapy.

“We will be working with our partner researchers worldwide across the RESTORE research consortium to directly put the findings of this study into further practice, and to explore the potential for a neural stem cell graft clinical trial in the future,” said Professor Pluchino.

Dr Catherine Godbold, Senior Research Communications Manager at the MS Society, said: “More than 150,000 people live with MS in the UK and it can be debilitating, exhausting and unpredictable. Neural stem cell therapy for MS is still in the very early stages of research, but these results with mice are invaluable.

“They help us understand how neural stem cells might one day be able to unlock desperately needed myelin-repair treatments. We’re proud to have supported this study and hope it can bring us another step closer to stopping progression for everyone with MS.” 

Funding

This work received funding from the Medical Research Council, the Bascule Charitable Trust, the National MS Society, FISM – Fondazione Italiana Sclerosi Multipla, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the UK MS Society Centre of Excellence.

About this genetics and multiple sclerosis research news

Author: Lucy Theobald
Source: University of Cambridge
Contact: Lucy Theobald – University of Cambridge
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Remyelination of the chronic demyelinated lesions of the spinal cord with directly induced Neural Stem Cells” by Stefano Pluchino et al. Brain

Disrupted Myelin Protein Implicated in Schizophrenia

 Ask your competent? doctor how much your myelin was damaged in your stroke and the EXACT PROTOCOLS TO FIX THAT!  Doesn't know anything? Fire them!

myelin (77 posts to April 2011)

Disrupted Myelin Protein Implicated in Schizophrenia

Summary: A new study has identified the protein hnRNP A1 as a key player in the production and maintenance of myelin, the fatty sheath that insulates nerve fibers in the brain. Myelin loss is common in disorders like multiple sclerosis and schizophrenia, and this research shows that hnRNP A1 disruptions can impair myelination at the molecular level, even before behavioral symptoms appear.

Using a rodent model, scientists induced and later reversed demyelination to track the effects on memory, motor function, and social behavior. The findings offer fresh insight into how early molecular changes in myelin-related proteins could contribute to neurodegenerative and neuropsychiatric disorders, potentially opening new avenues for therapeutic intervention.

Key Facts:

• Myelin Disruption: Disruption of hnRNP A1 impairs myelin production and may play a role in schizophrenia and multiple sclerosis.
• Silent Molecular Shifts: Changes in myelin-related proteins occurred without immediate behavioral symptoms, suggesting early markers of disease.
• Reversibility Observed: Restoring myelin reversed behavioral deficits in rodents, underscoring therapeutic potential.

Source: FAPESP

Research published in the Journal of Neurochemistry has detailed the role of a protein, hnRNP A1, in the formation and stability of myelin, suggesting an important impact on neurodegenerative diseases and mental disorders such as multiple sclerosis and schizophrenia.

The findings pave the way for new research and potential treatments.

Myelin is a fatty substance produced by oligodendrocytes (cells of the central nervous system) that forms a sheath, like a kind of “insulator.”

It “protects” the extensions of neurons (axons) and increases the conduction speed of nerve impulses that carry information between neural cells.

Scientific literature has shown that patients with multiple sclerosis and schizophrenia lose myelin (called demyelination), leaving part of the axons “unplugged” and causing damage to brain function.

This rodent study examined changes in proteins essential for myelin production (myelination). The results highlight the involvement of hnRNP A1 in maintaining the integrity of this protective sheath.

hnRNP A1 regulates the processing of messenger RNA, i.e., it controls how the molecule is cut and assembled (splicing), thereby determining which proteins are produced and in what amounts. Studied for years by this group of scientists at the State University of Campinas (UNICAMP), in the state of São Paulo, Brazil, hnRNP A1 had already figured prominently in previous research carried out on brain tissue from people with schizophrenia and on cells grown in the laboratory.

“When I was a master’s student, I worked with oligodendrocyte predecessor cell lines and their responses to antipsychotics. This protein, hnRNP A1, always appeared. We decided to try to understand its role in oligodendrocytes.

“But to do this, we had to use an animal model to induce myelination and understand the process,” explains Caroline Brandão Teles, first author of the article and FAPESP doctoral fellow at the Institute of Biology (IB-UNICAMP).

For researcher Fernanda Crunfli, also from IB-UNICAMP and corresponding author of the paper, myelin has been an important target of study for neuropsychiatric diseases.

“We were able to analyze the demyelination process in the animals and then restore the myelin sheath. This allowed for an interesting study window.

“We did behavioral tests to assess locomotion, short- and long-term memory, and social interaction. When the myelin is restored, all these functions return to the brain,” says Crunfli, who was a FAPESP postdoctoral fellow.

Teles points out that this was one of the results that caught the group’s attention – the fact that the changes were detected at the molecular level, without affecting the animals’ behavior.

“With this molecular and non-behavioral alteration, the work has the interesting potential to pinpoint an important protein in the establishment of schizophrenia. This same animal model is analyzed in research on multiple sclerosis, for example, and when there’s a behavioral study, changes are noted.

“In the case of schizophrenia, the fact that the behavior isn’t altered indicates, in my opinion, that this protein is essential in the development of the disease and may have an influence on its genesis,” Professor Daniel Martins-de-Souza, from IB-UNICAMP, Teles’ supervisor and head of the Neuroproteomics Laboratory, told Agência FAPESP.

Schizophrenia is a mental disorder characterized by loss of contact with reality (psychosis), hallucinations, delusions, and impaired cognition, among other symptoms. The exact cause is still unknown, but recent research suggests a combination of hereditary factors and molecular and functional alterations in the brain. Treatment includes antipsychotic medications and psychotherapy.

It is estimated that approximately 1.6 million people in Brazil have schizophrenia. Worldwide, the prevalence is about 1% of the world’s population.

For years, Martins-de-Souza’s research group has been working to understand the role of oligodendrocytes in schizophrenia and has managed to map a series of brain proteins that help to unravel the molecular basis of the disorder.

To understand the research

The group used a rodent (murine) model that has also been studied in cases of multiple sclerosis, a disease characterized by severe demyelination.

From the eighth week of the experiment, demyelination was induced and continued for another five weeks. The process was then interrupted and the myelin sheath was restored.

During this time, the researchers analyzed the activity of hnRNP A1. “We saw that the proteins linked to myelin in these animals were all reduced. By disrupting the activity of this protein [hnRNP A1], we ended up disrupting myelination,” says Teles.

The scientists believe that studying the impact of the protein’s alterations on synaptic transmission and cognitive processes could reveal new therapeutic targets.

Funding: In addition to the grants, the research was also supported by FAPESP through six other projects (17/25588-1, 19/05155-9, 18/01410-1, 23/08885-3, 18/01669-5 and 23/11514-7).

About this schizophrenia research news

Author: Heloisa Reinert
Source: FAPESP
Contact: Heloisa Reinert – FAPESP
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome” by Caroline Brandão Teles et al. Journal of Neurochemistry

Drug candidate restores myelin and leg mobility in multiple sclerosis mouse model

 Ask your competent? doctor if we need this post stroke for myelin problems. Doesn't know the answer. 

FIRE THAT INCOMPETENT DOCTOR!

If your doctor doesn't know anything about this, you don't have a functioning stroke doctor!

Drug candidate restores myelin and leg mobility in multiple sclerosis mouse model

An investigational drug for multiple sclerosis from Io Therapeutics has restored leg mobility and myelin nerve coatings in mice, the biotech announced Dec. 23.

The Texas-based company conducted the study, published in Acta Neuropathologica Communications, with a team of Canadian researchers led by George Robertson, Ph.D., from Dalhousie University in Nova Scotia.

Io now hopes to pursue the drug, called IRX4204, in multiple nervous system indications, CEO Martin Sanders, M.D., said in the release.

“The ability of IRX4204 to inhibit and functionally repair brain demyelination opens opportunities for potentially reparative treatment of brain damage in other types of neurologic conditions in which demyelination and microglial inflammation are demonstrated to play pathologic roles," Sanders said.

Related

Sanofi flunks midphase multiple sclerosis study, dealing another blow to Denali pact

The researchers induced experimental autoimmune encephalomyelitis (EAE) in the rodents, a common model for neuroinflammation in humans with MS. The disease is caused by the erosion of a protective sheath, made of myelin, that normally surrounds nerve cells. Without this protection, nerves degrade, leading to symptoms like muscle weakness, vision problems and cognitive issues, among others.

IRX4204 binds to and activates the retinoid X receptor (RXR), a hormone receptor known to be involved in myelin repair. A previous study found that the compound reduced pro-inflammatory T cells in mice with EAE.

The approved chemotherapy drug bexarotene also binds to RXR but is not recommended for use in multiple sclerosis after a phase 2 trial found it had poor efficacy and was not well tolerated by patients.

Light and Sound Therapy Maintains Myelin in Alzheimer’s

 

Doesn't your competent? doctor already have you using this? Oh, you DON'T HAVE A FUNCTIONING STROKE DOCTOR, DO YOU?

• 40 Hertz flickering light (2 posts to July 2021)

• 40Hz sensory stimulation (3 posts to March 2021)

 

Has your doctor verified that you had myelin damage from your stroke? What protocols are being used to fix such damage?  

Your competent? doctor and hospital need to ensure human testing gets done. I already bought a 40 Hertz light, not waiting decades before it is confirmed in humans.

This one mentions a 60 Hertz flickering light so ask your competent? doctor which one is better. No knowledge of either is a fireable offense!

Repeated Ketamine Anesthesia Restarts Plasticity in the Brain July 2021

 

 

Light and Sound Therapy Maintains Myelin in Alzheimer’s

Summary: A new study finds that 40Hz light and sound therapy helps maintain myelin, a crucial brain structure, in Alzheimer’s patients. This therapy, which protects neurons and supports brain function, could offer new treatment avenues for neurodegenerative diseases.

Researchers discovered that this stimulation enhances neural connections and reduces harmful inflammation. The therapy also shows potential for treating other conditions involving myelin loss, such as multiple sclerosis.

Key Facts:

1. 40Hz sensory stimulation preserves myelin in Alzheimer’s patients.
2. The therapy enhances neural connections and reduces inflammation.
3. Potential applications include treatment for multiple sclerosis.
4. Source: Picower Institute at MIT

Early-stage trials in Alzheimer’s disease patients and studies in mouse models of the disease have suggested positive impacts on pathology and symptoms from exposure to light and sound presented at the “gamma” band frequency of 40 Hz.

A new study zeroes in on how 40Hz sensory stimulation helps to sustain an essential process in which the signal-sending branches of neurons, called axons, are wrapped in a fatty insulation called myelin. Often called the brain’s “white matter,” myelin protects axons and insures better electrical signal transmission in brain circuits.

Amorim and Tsai’s team found that 40Hz light and sound not only preserved myelination in the brains of cuprizone-exposed mice, it also appeared to protect oligodendrocytes (the cells that myelinate neural axons), sustain the electrical performance of neurons, and preserve a key marker of axon structural integrity. Credit: Neuroscience News

“Previous publications from our lab have mainly focused on neuronal protection,” said Li-Huei Tsai, Picower Professor in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT and senior author of the new study in Nature Communications. Tsai also lead’s MIT’s Aging Brain Initiative. “But this study shows that it’s not just the gray matter, but also the white matter that’s protected by this method.”

This year Cognito Therapeutics, the spin-off company that licensed MIT’s sensory stimulation technology, published phase II human trial results in the Journal of Alzheimer’s Disease indicating that 40Hz light and sound stimulation significantly slowed the loss of myelin in volunteers with Alzheimer’s.

Also this year Tsai’s lab published a study showing that gamma sensory stimulation helped mice withstand neurological effects of chemotherapy medicines, including by preserving myelin. In the new study, members of Tsai’s lab led by former postdoc Daniela Rodrigues Amorim used a common mouse model of myelin loss—a diet with the chemical cuprizone— to explore how sensory stimulation preserves myelination.

Amorim and Tsai’s team found that 40Hz light and sound not only preserved myelination in the brains of cuprizone-exposed mice, it also appeared to protect oligodendrocytes (the cells that myelinate neural axons), sustain the electrical performance of neurons, and preserve a key marker of axon structural integrity.

When the team looked into the molecular underpinnings of these benefits, they found clear signs of specific mechanisms including preservation of neural circuit connections called synapses; a reduction in a cause of oligodendrocyte death called “ferroptosis;” reduced inflammation; and an increase in the ability of microglia brain cells to clean up myelin damage so that new myelin could be restored.

“Gamma stimulation promotes a healthy environment,” said Amorim who is now a Marie Curie Fellow at the University of Galway in Ireland. “There are several ways we are seeing different effects.”

The findings suggest that gamma sensory stimulation may help not only Alzheimer’s disease patients but also people battling other diseases involving myelin loss, such as multiple sclerosis, the authors wrote in the study.

Maintaining myelin

To conduct the study, Tsai and Amorim’s team fed some male mice a diet with cuprizone and gave other male mice a normal diet for six weeks. Halfway into that period, when cuprizone is known to begin causing its most acute effects on myelination, they exposed some mice from each group to gamma sensory stimulation for the remaining three weeks.

In this way they had four groups: completely unaffected mice, mice that received no cuprizone but did get gamma stimulation, mice that received cuprizone and constant (but not 40Hz) light and sound as a control, and mice that received cuprizone and also gamma stimulation.

After the six weeks elapsed, the scientists measured signs of myelination throughout the brains of the mice in each group. Mice that weren’t fed cuprizone maintained healthy levels, as expected. Mice that were fed cuprizone and didn’t receive 40Hz gamma sensory stimulation showed drastic levels of myelin loss.

Cuprizone-fed mice that received 40Hz stimulation retained significantly more myelin, rivaling the health of mice never fed cuprizone by some, but not all, measures.

The researchers also looked at numbers of oligodendrocytes to see if they survived better with sensory stimulation. Several measures revealed that in mice fed cuprizone, oligodendrocytes in the corpus callosum region of the brain (a key point for the transit of neural signals because it connects the brain’s hemispheres) were markedly reduced. But in mice fed cuprizone and also treated with gamma stimulation, the number of cells were much closer to healthy levels.

Electrophysiological tests among neural axons in the corpus callosum showed that gamma sensory stimulation was associated with improved electrical performance in cuprizone-fed mice who received gamma stimulation compared to cuprizone-fed mice left untreated by 40Hz stimulation.

And when researchers looked in the anterior cingulate cortex region of the brain, they saw that MAP2, a protein that signals the structural integrity of axons, was much better preserved in mice that received cuprizone and gamma stimulation compared to cuprizone-fed mice who did not.

Molecular mechanisms

A key goal of the study was to identify possible ways in which 40Hz sensory stimulation may protect myelin.

To find out, the researchers conducted a sweeping assessment of protein expression in each mouse group and identified which proteins were differentially expressed based on cuprizone diet and exposure to gamma frequency stimulation. The analysis revealed distinct sets of effects between the cuprizone mice exposed to control stimulation and cuprizone-plus-gamma mice.

A highlight of one set of effects was the increase in MAP2 in gamma-treated cuprizone-fed mice. A highlight of another set was that cuprizone mice who received control stimulation showed a substantial deficit in expression of proteins associated with synapses. The gamma-treated cuprizone-fed mice did not show any significant loss, mirroring results in a 2019 Alzheimer’s 40Hz study that showed synaptic preservation.

This result is important, the researchers wrote, because neural circuit activity, which depends on maintaining synapses, is associated with preserving myelin. They confirmed the protein expression results by looking directly at brain tissues.

Another set of protein expression results hinted at another important mechanism: ferroptosis. This phenomenon, in which errant metabolism of iron leads to a lethal buildup of reactive oxygen species in cells, is a known problem for oligodendrocytes in the cuprizone mouse model.

Among the signs was an increase in cuprizone-fed, control stimulation mice in expression of the protein HMGB1, which is a marker of ferroptosis-associated damage that triggers an inflammatory response. Gamma stimulation, however, reduced levels of HMGB1.

Looking more deeply at the cellular and molecular response to cuprizone demyelination and the effects of gamma stimulation, the team assessed gene expression using single-cell RNA sequencing technology.

They found that astrocytes and microglia became very inflammatory in cuprizone-control mice but gamma stimulation calmed that response. Fewer cells became inflammatory and direct observations of tissue showed that microglia became more proficient at clearing away myelin debris, a key step in effecting repairs.

The team also learned more about how oligodendrocytes in cuprizone-fed mice exposed to 40Hz sensory stimulation managed to survive better. Expression of protective proteins such as HSP70 increased and as did expression of GPX4, a master regulator of processes that constrain ferroptosis.

In addition to Amorim and Tsai, the paper’s other authors are Lorenzo Bozzelli, TaeHyun Kim, Liwang Liu, Oliver Gibson, Cheng-Yi Yang, Mitch Murdock, Fabiola Galiana-Meléndez, Brooke Schatz, Alexis Davison, Md Rezaul Islam, Dong Shin Park, Ravikiran M. Raju, Fatema Abdurrob, Alissa J. Nelson, Jian Min Ren, Vicky Yang and Matthew P. Stokes.

Funding: Fundacion Bancaria la Caixa, The JPB Foundation, The Picower Institute for Learning and Memory, the Carol and Gene Ludwig Family Foundation, Lester A. Gimpelson, Eduardo Eurnekian, The Dolby Family, Kathy and Miguel Octavio, the Marc Haas Foundation, Ben Lenail and Laurie Yoler, and the National Institutes of Health provided funding for the study.

About this neurology and neuroscience research news

Author: David Orenstein
Source: Picower Institute at MIT
Contact: David Orenstein – Picower Institute at MIT
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Multisensory gamma stimulation mitigates the effects of demyelination induced by cuprizone in male mice” by Li-Huei Tsai et al. Nature Communications

New Multiple Sclerosis Drug Regenerates Myelin, Improves Movement

 Does your competent? doctor and hospitals have enough functioning neurons to see this as a possibility for lost myelin during your stroke? Or don't you have a functioning stroke doctor or hospital?

Ask your doctor point blank. 'Does stroke cause demylination?' If it does then what is your doctor doing to get it repaired?

• myelin (74 posts to April 2011)

 

But there is also this:

Pregnancy Hormone Estriol May Reverse Myelin Damage in Multiple Sclerosis

 June 2023

And this:

 Antihistamine Sparks Hope for Myelin Repair in Multiple Sclerosis June 2023

 

The latest here:

New Multiple Sclerosis Drug Regenerates Myelin, Improves Movement

Summary: A new drug, PIPE-307, shows promise in reversing multiple sclerosis (MS) damage by promoting myelin regeneration around nerve cells, potentially restoring movement and function.

Developed by researchers, this innovative therapy targets a specific receptor, M1R, and has already demonstrated success in animal models. PIPE-307 is currently in Phase II clinical trials, offering hope for a groundbreaking treatment that could stop and even heal the damage caused by MS.

This novel approach could transform the future of MS therapy by addressing both symptoms and underlying damage.

Key Facts

1. Myelin Restoration: PIPE-307 stimulates myelin regeneration, potentially reversing MS-related nerve damage.
2. Targeted Action: The drug precisely targets the M1R receptor, enhancing its effectiveness in treating MS.
3. Clinical Trials: PIPE-307 is in Phase II trials, showing potential as a transformative MS treatment.

Source: UCSF

Multiple sclerosis (MS) degrades the protective insulation around nerve cells, leaving their axons, which carry electrical impulses, exposed like bare wires. This can cause devastating problems with movement, balance and vision; and without treatment, it can lead to paralysis, loss of independence and a shortened lifespan.

Now, scientists at UC San Francisco and Contineum Therapeutics have developed a drug that spurs the body to replace the lost insulation, which is called myelin. If it works in people, it could be a way to reverse the damage caused by the disease.  

The original breakthrough came when Chan invented a method to screen drugs for their ability to instigate remyelination. Credit: Neuroscience News

The new therapy, called PIPE-307, targets an elusive receptor on certain cells in the brain that prompts them to mature into myelin-producing oligodendrocytes. Once the receptor is blocked, the oligodendrocytes spring into action, wrapping themselves around the axons to form a new myelin sheath.

It was crucial to prove that the receptor, known as M1R, was present on the cells that can repair damaged fibers. Contineum scientist and first author Michael Poon, PhD, figured this out using a toxin found in green mamba snake venom. 

The work, which appears Aug. 2 in PNAS, caps a decade of work by UCSF scientists Jonah Chan, PhD,  and Ari Green, MD. Chan led the team to discover in 2014 that an obscure antihistamine known as clemastine could induce remyelination, which no one knew was possible. 

“Ten years ago, we discovered one way that the body can regenerate its myelin in response to the right molecular signal, winding back the consequences of MS,” said Chan, a Debbie and Andy Rachleff Distinguished Professor of Neurology at UCSF and senior author of the paper. “By carefully studying the biology of remyelination, we’ve developed a precise therapy to activate it – the first of a new class of MS therapies.”

A dirty drug creates a clean opening

The original breakthrough came when Chan invented a method to screen drugs for their ability to instigate remyelination. The screen identified a group drugs, including clemastine, that had one thing in common: they blocked muscarinic receptors.  

Clemastine’s benefits begin with its effect on oligodendrocyte precursor cells (OPCs). These cells stay dormant in the brain and spinal cord until they sense injured tissue. Then they move in and give rise to oligodendrocytes, which produce myelin. 

For some reason during MS, OPCs gather around decaying myelin but fail to rebuild it. Chan figured out that clemastine activated OPCs by blocking muscarinic receptors, enabling the OPCs to mature into myelin-producing oligodendrocytes.

Nerves and their myelin are notoriously hard to repair, whether due to MS, dementia or other injury. Green and Chan carried out a trial of clemastine in patients with MS, and it was a success – the first time that a drug showed the capacity to restore the myelin lost in MS. Despite being safe to use, however, clemastine was only modestly effective. 

“Clemastine is not a targeted drug, affecting several different pathways in the body,” said Green, Chief of the Division of Neuroimmunology and Glial Biology in the UCSF Department of Neurology and co-author of the paper. “But from the get-go, we saw that its pharmacology with muscarinic receptors could point us toward the next generation of restorative therapies in MS.” 

A snake venom toxin illuminates the right target

The researchers continued using clemastine to understand the curative potential of regenerating myelin in MS. They developed a series of tools to monitor remyelination, both in animal models of MS and in MS patients, showing that the benefits seen with clemastine came from remyelination – and pointing the way for how new drugs should be tested and evaluated.

They also found that clemastine’s benefits came from blocking just one of the five muscarinic receptors, M1R, but the effect on M1R was middling, and the drug also affected the other receptors. The ideal drug would need to zero in on M1R.

At this point, the UCSF scientists needed an industry partner to advance the project. Ultimately, Contineum Therapeutics (then known as Pipeline Therapeutics) was formed to take a meticulous approach to creating that ideal drug. Chan and Green helped the company confirm that M1R was the right target for a remyelinating drug, and then make a drug that blocked it exclusively.

Poon, a biologist at Contineum, realized that MT7, a toxin found in the venom of the deadly green mamba snake, could reveal exactly where M1R was in the brain.

“We needed to prove, beyond doubt, that M1R was present in OPCs that were near the damage caused by MS,” Poon said. “MT7, which is exquisitely selective for M1R, fit the bill.”

Poon used MT7 to engineer a molecular label for M1R that revealed rings of OPCs gathering around damage in a mouse model of MS and in human MS tissue. 

Developing a clinic-ready drug

A team of medicinal chemists at Contineum, led by Austin Chen, PhD, then got to work on the drug that Chan and Green envisioned, designing PIPE-307 to potently block M1R and get into the brain.

The researchers tested the effects of the new drug on OPCs grown in petri dishes and the animal models of MS using Chan’s and Green’s methods for tracking remyelination. PIPE-307 blocked the M1R receptor much better than clemastine; prompted OPCs to mature into oligodendrocytes and begin myelinating nearby axons; and it crossed the blood-brain barrier.

But most tellingly, it reversed the degradation seen in a mouse model of MS.

“A drug might seem to work in these abstract scenarios, affecting the right receptor or cell, but the key finding was actual recovery of nervous system function,” Chan said. 

In 2021, PIPE-307 passed a Phase I clinical trial, demonstrating its safety. It is currently being tested in MS patients in Phase II. 

If it succeeds, it could transform how MS is treated. 

“Every patient we diagnose with MS comes in with some degree of pre-existing injury,” Green said. “Now we might have a chance to not just stop their disease, but to also heal.”

Other authors are Kym I Lorrain, Karin J Stebbins, Geraldine C Edu, Alexander R Broadhead, Ariana J Lorenzana, Jeffrey R Roppe, Jill M Baccei, Christopher S Baccei, and Daniel S Lorrain, all employees of Contineum Therapeutics.

Funding: The work was partially funded by the NIH/National Institute of Neurological Disorders and Stroke (grants R01NS115746 and R01MH125515). 

Disclosures: All Contineum Therapeutics employees hold financial shares of the company. Chan and Green also hold financial shares in Contineum Therapeutics but no longer serve in any role. Contineum Therapeutics owns patent rights to PIPE-307.

About this multiple sclerosis and neuropharmacology research news

Author: Levi Gadye
Source: UCSF
Contact: Levi Gadye – UCSF
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Targeting the muscarinic M1 receptor with a selective, brain-penetrant antagonist to promote remyelination in multiple sclerosis” by Jonah Chan et al. PNAS

Growth hormone promotes myelin repair after chronic hypoxia via triggering pericyte-dependent angiogenesis

 Ask you competent? doctor if you need myelin repair post stroke, and don't accept not knowing as an answer. YOUR FUCKING DOCTOR IS SUPPOSED TO BE COMPETENT! Only over a decade for your doctor to become competent in myelin!

In here is both myelin repair topics and whether stroke causes myelin damage.

• myelin (73 posts to April 2011)

Growth hormone promotes myelin repair after chronic hypoxia via triggering pericyte-dependent angiogenesis

• Shu-Yu Ren ¹⁰
• Yu Xia ¹⁰
• Bin Yu
• 
  
• Lan Xiao
• Zhang-Xue Hu
• Feng Mei ¹¹
• Show all authors
• Show footnotes

Published:April 22, 2024DOI:https://doi.org/10.1016/j.neuron.2024.03.026

Highlights

• •
  GH treatment promotes myelin repair and functional recovery after hypoxia
• •
  GHR is selectively expressed by a subpopulation of pericytes
• •
  GHR-positive pericyte-tip cells lead blood vessel bridging and branching
• •
  GHR-positive pericytes modulate angiogenesis and govern myelination indirectly

Summary

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.

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