Stem Cells Repair Mouse Brains Post-Stroke

This image shows a coronal section through the mouse brain after stroke and neural stem cell transplantation. The dashed circle indicates the stroke area. The neurite projections of the transplanted human cells are stained in dark brown. Neurites extend locally into the cortex (CX) but also via the corpus callosum (CC) into the other brain hemisphere.
Image Credit: Universität Zürich

Stem cell transplantation can reverse stroke damage, researchers at the University of Zurich report. Its beneficial effects include regeneration of neurons and restoration of motor functions, marking a milestone in the treatment of brain disorders.

One in four adults suffer a stroke in their lifetime, leaving around half of them with residual damage such as paralysis or speech impairment because internal bleeding or a lack of oxygen supply kills brain cells irreversibly. No therapies currently exist to repair this kind of damage. “That’s why it is essential to pursue new therapeutic approaches to potential brain regeneration after diseases or accidents,” says Christian Tackenberg, the Scientific Head of Division in the Neurodegeneration Group at the University of Zurich (UZH) Institute for Regenerative Medicine.

Neural stem cells have the potential to regenerate brain tissue, as a team led by Tackenberg and postdoctoral researcher Rebecca Weber has now compellingly shown in two studies that were conducted in collaboration with a group headed by Ruslan Rust from the University of Southern California. “Our findings show that neural stem cells not only form new neurons, but also induce other regeneration processes,” Tackenberg says.

Mystery solved: New study reveals how DNA repair genes play a major role in Huntington's disease

Dr. Xiangdong William Yang
Photo Credit: Courtesy of UCLA/Health

A new UCLA Health study has discovered in mouse models that genes associated with repairing mismatched DNA are critical in eliciting damages to neurons that are most vulnerable in Huntington's disease and triggering downstream pathologies and motor impairment, shedding light on disease mechanisms and potential new ways to develop therapies. 

Huntington’s disease is one of the most common inherited neurodegenerative disorders that typically begins in adulthood and worsens over time. Patients begin to lose neurons in specific regions of the brain responsible for movement control, motor skill learning, language and cognitive function. Patients typically live 15 to 20 years after diagnosis with symptoms worsening over time. There is no known cure or therapy that alters the course of the disease.

The cause of Huntington's disease was discovered over three decades ago--a "genetic stutter" mutation involves repeats of three letters of the DNA, cytosine-adenine-guanine (CAG), in a gene called huntingtin. Healthy individuals usually have 35 or fewer CAG repeats, but people inherited with mutation of 40 or more repeats will develop the disease. The more CAG repeats a person inherits, the earlier the disease onset occurs. However, how the mutation causes the disease remains poorly understood. 

Opening for a new type of drug for Alzheimer’s Disease

Kaj Blennow and Tohidul Islam.
Photo Credit: Johan Wingborg

A complementary drug to combat Alzheimer’s disease could target a specific part of the nerve cell protein tau. This is the finding of research from the University of Gothenburg, which also offers a better way to measure the effect of treatment among patients.

Researchers from the University of Gothenburg, together with colleagues from the University of Pittsburgh in the US, published their findings in the journal Nature Medicine.

The study provides insights into what happens during the earliest phase when the protein tau is transformed into thread-like strands (fibrils) in the nerve cells. This is one of the processes in Alzheimer’s disease and occurs alongside the formation of amyloid plaques. In healthy individuals, the protein tau stabilizes the tubular building blocks (microtubules) that make up the long projections of the nerve cells.

During the development of Alzheimer’s disease, tau undergoes pathological changes. First, tau forms small, soluble aggregates that are secreted from the nerve cells and are thought to be able to spread these changes to other nerve cells. The protein is then converted into larger, harmful, thread-like strands in the nerve cells.

Study reveals reasons for misdiagnosis of frontotemporal dementia

Researchers have discovered patterns in the misdiagnosis of frontotemporal dementia
Photo Credit: Anna Shvets

University of Queensland researchers discovered that nearly 70 per cent of suspected frontotemporal dementia patients ultimately did not have the disease, in a study aimed at identifying factors that contribute to misdiagnosis of this notoriously difficult to diagnose disorder.

Psychiatrist Dr Joshua Flavell, working with cognitive neurologist Professor Peter Nestor at the Mater Hospital Memory and Cognitive Disorders clinic and UQ’s Queensland Brain Institute, analyzed data from 100 patients suspected of having frontotemporal dementia who had been referred by specialist physicians like neurologists, psychiatrists or geriatricians.

“Of the 100 patients, 34 were true-positive, and 66 were false-positive for frontotemporal dementia,” Dr Flavell said.

“We found that misinterpretation of brain scans, particularly nuclear imaging, led to 32 patients being incorrectly diagnosed.

How Does the Brain Differentiate New Stimuli from Old Ones?

The illustration represents how sounds are encoded in the cerebral cortex, with neurons (at right) using "echoing" activity to track auditory stimuli to change and improve its predictions of the future.
Illustration Credit: Yuriy Shymkiv

The cerebral cortex is the largest part of a mammal’s brain, and by some measures the most important. In humans in particular, it’s where most things happen—like perception, thinking, memory storage, and decision-making. One current hypothesis suggests that the cortex’s primary role is to predict what’s going to happen in the future by identifying and encoding new information it receives from the outside world and comparing it with what was expected to occur.

A new study published today in the journal Neuron takes a big step toward proving that hypothesis. The paper’s lead author is Yuriy Shymkiv, a postdoctoral fellow in the lab of Professor Rafael Yuste.

“We found that the cortex acts like a memory machine, encoding new experiences, and predicting the very near future,” Shymkiv said.

Research in Fruit Flies Pinpoints Brain Pathways Involved in Alcohol-Induced Insomnia

Adrian Rothenfluh, PhD (left), and Maggie Chvilicek (right), authors on the recent study.
Photo Credit: Courtesy of University of Utah Health

Alcohol use disorder, which affects over 10% of Americans, can lead to persistent and serious insomnia. Difficulties falling asleep and staying asleep can last even after months of sobriety, increasing the risk of relapse. But treating withdrawal-related insomnia is difficult, partly because what’s going on in the brain in this condition remains largely mysterious.

 Now, research in fruit flies has identified specific brain signals and groups of brain cells that are involved in alcohol-induced insomnia. This work could ultimately lead to targeted treatments for alcohol-related sleep loss, helping people recover from alcohol use disorder.

  “The effects of alcohol on sleep seem to be localized to a particular cell type in the brain, which is not something that’s ever been shown before,” says Maggie Chvilicek, graduate researcher in neuroscience at the University of Utah and lead author on the study. She adds that these cells often do similar things in flies and humans. “The mechanism that we identified is something that very likely could also exist in a mammalian brain.”

Improved Brain Decoder Holds Promise for Communication in People with Aphasia

Brain activity like this, measured in an fMRI machine, can be used to train a brain decoder to decipher what a person is thinking about. In this latest study, UT Austin researchers have developed a method to adapt their brain decoder to new users far faster than the original training, even when the user has difficulty comprehending language.
Image Credit: Jerry Tang/University of Texas at Austin.

People with aphasia — a brain disorder affecting about a million people in the U.S. — struggle to turn their thoughts into words and comprehend spoken language.

A pair of researchers at The University of Texas at Austin has demonstrated an AI-based tool that can translate a person’s thoughts into continuous text, without requiring the person to comprehend spoken words. And the process of training the tool on a person’s own unique patterns of brain activity takes only about an hour. This builds on the team’s earlier work creating a brain decoder that required many hours of training on a person’s brain activity as the person listened to audio stories. This latest advance suggests it may be possible, with further refinement, for brain computer interfaces to improve communication in people with aphasia.

“Being able to access semantic representations using both language and vision opens new doors for neurotechnology, especially for people who struggle to produce and comprehend language,” said Jerry Tang, a postdoctoral researcher at UT in the lab of Alex Huth and first author on a paper describing the work in Current Biology. “It gives us a way to create language-based brain computer interfaces without requiring any amount of language comprehension.”

Cutting edge technology shows promise in tackling deadly brain tumors

Delivering advanced gene-editing tools directly to the tumor site can improve the body’s defense against glioblastoma
Image Credit: Gemini

A new study led by Khuloud Al Jamal, Professor of Drug Delivery & Nanomedicine, has found an innovative strategy to combat glioblastoma (GB), a fast-growing and aggressive type of brain tumor.

GB is a brain tumor originating in the brain or spinal cord. Despite advances in cancer treatment, it can remain resistant to therapies, including immune checkpoint (ICP) blockade therapies. ICP blockade works by targeting specific proteins on immune or tumor cells to prevent tumors from evading the immune system. While effective in other cancers, this approach has shown limited success in treating GB. The is due to complex interactions between immune cells and glioblastoma stem cells (GSCs), which suppress the immune response and reduce the effectiveness of these therapies.

In the study, published in Advanced Science, Professor Al Jamal and her team revealed how they have taken a novel approach to overcome this challenge by focusing on the mesenchymal subtype of GSCs, which is particularly aggressive and therapy resistant. The study employed lipid nanoparticles (LNPs) — tiny, fat-based carriers — to transport CRISPR RNAs, an advanced gene-editing tool, to GSC and immune cells in therapeutically relevant tumor models. 

Spinal cord stimulation: A transformative option for chronic pain management

Image Credit: cottonbro studio

Chronic back and lower extremity pain are leading causes of disability worldwide, significantly impacting the quality of life and productivity of the patients affected by them. For these patients, spinal cord stimulation (SCS) — a non-pharmacological, neurostimulation treatment that involves the surgical implantation of electrodes and a power source to deliver electrical current to the spinal cord to reduce pain signals to the brain — offers an advanced, safe and minimally invasive treatment option.

SCS is not a new medical technology, but has evolved considerably since its introduction in the 1960s. “It was historically used for patients who had undergone spine surgery but continued to experience pain,” explains Jonathan Droessler, MD, a specialist in interventional physiatry at UCLA’s Department of Orthopedic Surgery.

“Today, it’s used for patients with intractable pain lasting more than six months.”

Videos with Cold Symptoms Activate Brain Regions and Trigger Immune Response

 Study on Brain Activity and Antibody Concentration
Photo Credit: Andrea Piacquadio

People who watch videos of sneezing or sick people show increased activity in brain regions that represent an interface between the brain and the immune system and react to potential dangers. At the same time, the concentration of antibodies in their saliva increases. The findings of a study by researchers from the Department of Biology at the University of Hamburg indicate that an important part of the immune system responds even before a pathogen enters the body. The results were published in the journal Brain Behavior and Immunity.

Throughout human history, communicable diseases, especially viral respiratory infections such as SARS-CoV-2 or influenza, have been among the main factors that significantly influence human mortality. The constant threat of pathogen transmission has led to the development of various physiological mechanisms of the immune system - for example, the body releases proteins to fight pathogens in the body.

Self-Assembling Cerebral Blood Vessels: A Breakthrough in Alzheimer’s Treatment

Image Credit: Courtesy of Pohang University of Science and Technology

A 3D model accurately mimicking the Blood-Brain Barrier (BBB) in a laboratory environment has been successfully developed by research teams led by Professor Jinah Jang from the Departments of Mechanical Engineering, Life Sciences, IT Convergence Engineering, and the Graduate School of Convergence at POSTECH, and Professor Sun Ha Paek from the Department of Neurosurgery at Seoul National University Hospital. This study was recently published in Biomaterials Research, an international academic journal on materials science.

Neurodegenerative diseases, including Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), result from the progressive decline of brain and nervous system functions, primarily due to aging. Chronic neuroinflammation, a key driver of these disorders, arises from the intricate interactions between cerebral blood vessels and neural cells, where the BBB plays a pivotal regulatory role. However, existing BBB models have been unable to replicate the complex three-dimensional 3D structure of cerebral blood vessels, posing significant challenges for research and drug development.

Regulatory T Cells Found to Safeguard Brain Health, Memory Formation

Differences in neuronal activation in mice with intact Tregs (left) and depleted Tregs (right). The finding demonstrates that Tregs play a role in ensuring healthy neuronal activity under normal conditions.
Image Credit: Mathis/Benoist Lab

Immune cells called regulatory T cells have long been known for their role in countering inflammation. In the setting of infection, these so-called Tregs restrain the immune system to ensure it doesn’t go into overdrive and mistakenly attack the body’s own organs.

Now scientists at Harvard Medical School have discovered a distinct population of Tregs dwelling in the protective layers of the brains of healthy mice with a repertoire much broader than inflammation control.

The research, published Jan. 28 in Science Immunology, shows that these specialized Tregs not only control access to the inner regions of the brain but also ensure the proper renewal of nerve cells in an area of the brain where short-term memories are formed and stored.

The research, funded in part by the National Institutes of Health, represents an important step toward untangling the complex interplay of immune cells in the brain. If replicated in further animal studies and confirmed in humans, the research could open up new avenues for averting or mitigating disease-fueling inflammation in the brain.

Researchers detect that people with schizophrenia have an altered ability to visually perceive contrast

UB researchers Cristina de la Malla and Daniel Linares.
Photo Credit: Courtesy of University of Barcelona

According to a review of more than 600 studies, these patients would have difficulty in detecting differences in light intensity between adjacent areas, without which they cannot adequately see their surroundings and objects.

The article, published in the journal Schizophrenia Bulletin, is signed by researchers Daniel Linares and Cristina de la Malla, together with master’s student Aster Joostens, from the Vision and Control of Action Group of the Faculty of Psychology and the UB Institute of Neurosciences (UBneuro).

A key indicator of visual function

The symptoms of schizophrenia are characterized by alterations in thinking and behavior, such as loss of contact with reality, delusions or hallucinations, but there are also abnormalities in the perception of visual stimuli, such as deficits in the perception of color or contrast. Understanding these abnormalities may provide clues as to how information processing disturbances contribute to the characteristic symptoms of schizophrenia. “Contrast perception is one of the most fundamental abilities of vision, as without it, we cannot adequately perceive the environment and the objects in it, which can compromise everyday tasks such as moving through space, recognizing faces or reading”, explains the research team, part of the Department of Cognition, ​​​​​​​Development and Educational Psychology.

Gene editing extends lifespan in mouse model of prion disease

Broad Communications Eric Minikel and Sonia Vallabh run a lab with a singular focus: preventing and treating prion disease within their lifetime.
Photo Credit: Maria Nemchuk

Researchers at the Broad Institute of MIT and Harvard have developed a gene-editing treatment for prion disease that extends lifespan by about 50 percent in a mouse model of the fatal neurodegenerative condition. The treatment, which uses base editing to make a single-letter change in DNA, reduced levels of the disease-causing prion protein in the brain by as much as 60 percent. 

There is currently no cure for prion disease, and the new approach could be an important step towards treatments that prevent the disease or slow its progression in patients who have already developed symptoms. A base-editing approach could also likely be a one-time treatment for all prion disease patients regardless of the genetic mutation causing their disease. 

The work, led by Broad senior group leaders Sonia Vallabh and Eric Minikel, as well as Broad core institute member David Liu, is the first demonstration that lowering levels of the prion protein improves lifespan in animals that have been infected with a human version of the protein. The findings appear in Nature Medicine.

Unraveling the Mysteries of DNA Damage in the Brain

Immunofluorescent staining of mouse brain, showing neurons and glial cells in the hippocampus. Blue are cell nuclei, while green are microfilaments of the cell extensions. Red is a marker of DNA damage and is predominantly in the neurons.
Image Credit: Aris Polyzos/Berkeley Lab

Brain cells receive sensory inputs from the outside world and send signals throughout the body telling organs and muscles what to do. Although neurons comprise only 10% of brain cells, their functional and genomic integrity must be maintained over a lifetime. Most dividing cells in the body have well-defined checkpoint mechanisms to sense and correct DNA damage during DNA replication.

Neurons, however, do not divide. For this reason, they are at greater risk of accumulating damage and must develop alternative repair pathways to avoid dysfunction. Scientists do not understand how neuronal DNA damage is controlled in the absence of replication checkpoints.

A recent study led by Cynthia McMurray and Aris Polyzos in Lawrence Berkeley National Laboratory’s (Berkeley Lab’s) Molecular Biophysics and Integrated Bioimaging Division addressed this knowledge gap, shedding light on how DNA damage and repair occur in the brain. Their results suggest that DNA damage itself serves as the checkpoint, limiting the accumulation of genomic errors in cells during natural aging. The paper, published in Nature Communications, offers clues to understanding the potential role of unrepaired DNA damage in the progression of neurodegenerative diseases and could help inform the development of therapies.

Membrane Anchor Suppresses Protein Aggregation

3 D reconstruction of a microscope image: red is the membrane and green clumped prion protein.
Image Credit: AG Tatzelt

Researchers have gained valuable insight into the development of prion diseases of the brain.

Protein aggregation is typical of various neurodegenerative diseases such as Alzheimer’s, Parkinson’s and prion diseases such as Creutzfeld-Jakob disease. A research team headed by Professor Jörg Tatzelt from the Department of Biochemistry of Neurodegenerative Diseases at Ruhr University Bochum, Germany, has now used new in vitro and cell culture models to show that a lipid anchor on the outer membrane of nerve cells inhibits the aggregation of the prion protein. “Understanding the mechanisms that cause the originally folded proteins to transform into pathogenic forms is of crucial importance for the development of therapeutic strategies,” says Jörg Tatzelt. The team published their findings in the journal Proceedings of the National Academy of Sciences.

Researchers discover how to mimic hibernation in non-hibernating animals

OHSU researcher Domenico Tupone, Ph.D., has discovered a method to control human body temperature, mimicking hibernation in non-hibernating animals. His research is focused on how controlled hypothermia may reduce tissue damage following a cardiac attack or stroke.
Photo Credit: OHSU/Christine Torres Hicks

In the same way a bear instinctively lowers its body temperature to survive the winter’s chill, scientists have discovered a groundbreaking method to control human body temperature —potentially saving lives in emergency situations.

Oregon Health & Science University researchers have identified a process that could one day help clinicians lower body temperature in people experiencing life-threatening events, such as heart attacks or strokes.

If applied in humans, who can’t naturally hibernate, the discovery could mimic the natural ability of certain animals to lower their body temperature during hibernation.

“The idea is to reduce the body temperature to a lower level so that tissues like the brain or heart don't need as much oxygen, allowing them to survive the ischemia [lack of oxygen to tissues] longer and improve the functional outcomes of strokes or heart attacks,” said Domenico Tupone, Ph.D., senior author of the study and research assistant professor of neurological surgery in the OHSU School of Medicine.

Fueling nerve cell function and plasticity

The picture shows neurons (magenta) born in the adult mouse hippocampus. Nuclei are stained cyan. The extending dendrites are important sites where mechanisms of plasticity and competition for survival take place.
Photo Credit: Courtesy of ©Bergami Lab / University of Cologne

New finding from scientists at the University of Cologne discloses how mitochondria control tissue rejuvenation and synaptic plasticity in the adult mouse brain

Nerve cells (neurons) are amongst the most complex cell types in our body. They achieve this complexity during development by extending ramified branches called dendrites and axons and establishing thousands of synapses to form intricate networks. The production of most neurons is confined to embryonic development, yet few brain regions are exceptionally endowed with neurogenesis throughout adulthood. It is unclear how neurons born in these regions successfully mature and remain competitive to exert their functions within a fully formed organ. However, understanding these processes holds great potential for brain repair approaches during disease.

A team of researchers led by Professor Dr Matteo Bergami at the University of Cologne’s CECAD Cluster of Excellence in Aging Research addressed this question in mouse models, using a combination of imaging, viral tracing and electrophysiological techniques. They found that, as new neurons mature, their mitochondria (the cells’ power houses) along dendrites undergo a boost in fusion dynamics to acquire more elongated shapes. This process is key in sustaining the plasticity of new synapses and refining pre-existing brain circuits in response to complex experiences. The study ‘Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons’ has been published in the journal Neuron.

Autism and ADHD are linked to disturbed gut flora very early in life

The researchers have found links between the gut flora in babies first year of life and future diagnoses.
Photo Credit: Cheryl Holt

Disturbed gut flora during the first years of life is associated with diagnoses such as autism and ADHD later in life. This is according to a study led by researchers at the University of Florida and Linköping University and published in the journal Cell.

The study is the first forward-looking, or prospective, study to examine gut flora composition and a large variety of other factors in infants, in relation to the development of the children's nervous system. The researchers have found many biological markers that seem to be associated with future neurological development disorders, such as autism spectrum disorder, ADHD, communication disorder and intellectual disability.

“The remarkable aspect of the work is that these biomarkers are found at birth in cord blood or in the child’s stool at one year of age over a decade prior to the diagnosis,” says Eric W Triplett, professor at the Department of Microbiology and Cell Science at the University of Florida, USA, one of the researchers who led the study.

Chickadees are Memory Geniuses. Their Barcode-Like Neural Activity May Be to Thank.

Chickadee caching a seed overlaid with a neural ‘barcode’ activity
Image Credit: Columbia’s Zuckerman Institute

Black-capped chickadees have extraordinary memories that can recall the locations of thousands of morsels of food to help them survive the winter. Now scientists at Columbia's Zuckerman Institute have discovered how the chickadees can remember so many details: they memorize each food location using brain cell activity akin to a barcode. These new findings may shed light on how the brain creates memories for the events that make up our lives.

"We see the world through our memories of objects, places and people," said Dmitriy Aronov, PhD, a principal investigator at Columbia’s Zuckerman Institute and an assistant professor of neuroscience at Columbia’s Vagelos College of Physicians and Surgeons. "Memories entirely define the way we see and interact with the world. With this bird, we have a way to understand memory in an incredibly simplified way, and in understanding their memory, we will understand something about ourselves."

This barcode-like formatting of memory, revealed for the first time today in the journal Cell, may be a common tactic in animal brains, including those of humans. "There are many findings in humans that are totally consistent with a barcode mechanism," said postdoctoral research fellow Selmaan Chettih, PhD, the study's co-first author along with Emily Mackevicius, PhD.