Screening in zebrafish identifies a drug to potentially improve recovery from spinal cord injury

Zebra fish
Photo Credit: © Center for Regenerative Therapies Dresden / Technische Universität Dresden

Scientists from the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology, the University of Edinburgh, and the Research Institute of the McGill University Health Centre in Montreal, investigated potential drugs to improve recovery from spinal cord injury. After testing over a thousand molecules, they identified cimetidine, an existing drug, to improve spinal repair in zebrafish and mice. Their work uncovers a promising route to new treatments and highlights the potential of zebrafish to screen for molecules that aid in spinal repair. The work was published in the journal Theranostics.

Sudden impacts to the spinal cord, such as those caused by a car accident, can cause lifelong injuries. The healing of an injury can be prolonged or even prevented by inflammation caused by an overreaction of the body’s immune system. Reducing inflammation with existing anti-inflammatory drugs suppresses the immune response as a whole, inhibiting the immune cells that are beneficial and promote injury repair.

In a new study, scientists from the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology, the University of Edinburgh, and the Research Institute of the McGill University Health Centre tested more than a thousand drugs in zebrafish larvae for their ability to prevent excessive inflammation during an immune response. Through this screening process, the research team identified an existing drug – cimetidine – that improved spinal cord repair in zebrafish.

Brain receptor patterns separate sensory and cognitive networks

Receptor patterns define key organizational principles in the brain, scientists have discovered.
Photo Credit: Pete Linforth

An international team of researchers, studying macaque brains, have mapped out neurotransmitter receptors, revealing a potential role in distinguishing internal thoughts and emotions from those generated by external influences.

The comprehensive dataset has been made publicly available, serving as a bridge linking different scales of neuroscience - from the microscopic to the whole brain.

Lead author Sean Froudist-Walsh, from the University of Bristol’s Department of Computer Science explained: “Imagine the brain as a city. In recent years, brain research has been focused on studying its roads, but in this research, we've made the most detailed map yet of the traffic lights - the neurotransmitter receptors - that control information flow.

“We've discovered patterns in how these 'traffic lights' are arranged that help us understand their function in perception, memory, and emotion.

“It's like finding the key to a city's traffic flow, and it opens up exciting possibilities for understanding how the normal brain works.

“Potentially in the future, other researchers may use these maps to target particular brain networks and functions with new medicines.

Pregnancy hormone repairs myelin damage in MS mouse model

Photo Credit: Yassine Khalfalli

Treating a mouse model of multiple sclerosis with the pregnancy hormone estriol reversed the breakdown of myelin in the brain’s cortex, a key region affected in multiple sclerosis, according to a new UCLA Health study.

In multiple sclerosis, inflammation spurs the immune system to strip away the protective myelin coating around nerve fibers in the brain’s cortex, hampering electrical signals sent and received by the brain. Atrophy of the cortex in MS patients is associated with permanent worsening of disability, such as cognitive decline, visual impairment, weakness and sensory loss.

No currently available treatments for MS can repair damage to myelin. Instead, these treatments target inflammation to reduce symptom flare-ups and new nerve tissue scarring. Previous UCLA-led research found that estriol, a type of estrogen hormone produced in pregnancy, reduced brain atrophy and improved cognitive function in MS patients.

In the new study, researchers treated a mouse model of MS with estriol and found that it prevented brain atrophy and induced remyelination in the cortex, indicating that the treatment can repair damage caused by MS, rather than just slow the destruction of myelin.

Altered gut bacteria may be early sign of Alzheimer’s disease

 

Alzheimer’s disease causes changes to the brain that begin two decades or more before symptoms appear. A study by researchers at Washington University School of Medicine in St. Louis reveals that the bacteria that live in the gut also change before Alzheimer’s symptoms arise, a discovery that could lead to diagnostics or treatments for Alzheimer’s disease that target the gut microbiome.
Image Credit: Gerd Altmann

People in the earliest stage of Alzheimer’s disease — after brain changes have begun but before cognitive symptoms become apparent — harbor an assortment of bacteria in their intestines that differs from the gut bacteria of healthy people, according to a study by researchers at Washington University School of Medicine in St. Louis.

The findings, published June 14 in Science Translational Medicine, open up the possibility of analyzing the gut bacterial community to identify people at higher risk of developing dementia, and of designing microbiome-altering preventive treatments to stave off cognitive decline.

“We don’t yet know whether the gut is influencing the brain or the brain is influencing the gut, but this association is valuable to know in either case,” said co-corresponding author Gautam Dantas, PhD, the Conan Professor of Laboratory and Genomic Medicine. “It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to Alzheimer’s disease, in which case altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease.”

New study reveals strong connection between heart and brain health

A growing amount of evidence points to interactions between heart health and brain health.

Cardiovascular diseases serve as a crucial backdrop for brain diseases like stroke, dementia, cerebral small vessel disease and cognitive impairment. Studies have shown, for example, that atrial fibrillation, even in stroke-free individuals, is associated with an increased incidence of dementia and silent cerebral damage. Heart failure has been linked to cognitive impairment and dementia due to reduced cerebral blood flow caused by a failing heart. Conversely, mental disorders and negative psychological factors may contribute to the onset and progression of cardiovascular diseases. Individuals with conditions such as schizophrenia, bipolar disorder, epilepsy or depression are more prone to cardiovascular diseases.

Despite this growing knowledge, previous studies on heart-brain interactions and associated risk factors have been limited in scope, focusing on specific diseases or utilizing small sample sizes. Consequently, the overall understanding of the structural and functional links between the heart and brain remains incomplete.

A new study conducted by researchers from UNC-Chapel Hill, the University of Pennsylvania and Purdue University leverages large magnetic resonance imaging (MRI) data to shed light on the close relationship between cardiovascular diseases and brain diseases such as stroke, dementia and cognitive impairment, unraveling the underlying genetic signatures and inter-organ connections between the heart and brain.

AI helps show how the brain’s fluids flow

A video shows a perivascular space (area within white lines) into which the researchers injected tiny particles. The particles (shown as moving dots) are trailed by lines which indicate their direction. Having measured the position and velocity of the particles over time, the team then integrated this 2D video with physics-informed neural networks to create an unprecedented high-resolution, 3D look at the brain’s fluid flow system.
Video Credit: Douglas Kelley

New research targets diseases including Alzheimer’s.

A new artificial intelligence-based technique for measuring fluid flow around the brain’s blood vessels could have big implications for developing treatments for diseases such as Alzheimer’s.

The perivascular spaces that surround cerebral blood vessels transport water-like fluids around the brain and help sweep away waste. Alterations in the fluid flow are linked to neurological conditions, including Alzheimer’s, small vessel disease, strokes, and traumatic brain injuries but are difficult to measure in vivo.

A multidisciplinary team of mechanical engineers, neuroscientists, and computer scientists led by University of Rochester Associate Professor Douglas Kelley developed novel AI velocimetry measurements to accurately calculate brain fluid flow. The results are outlined in a study published by Proceedings of the National Academy of Sciences.

UC Irvine neuroscientists develop ‘meta-cell’ to move Alzheimer’s fight forward

A research team led by Vivek Swarup, UCI assistant professor of neurobiology and behavior, has developed a new process for creating a “meta-cell” that will advance the understanding of gene processes within individual cells.
Photo Credit: UCI School of Biological Sciences

University of California, Irvine neuroscientists probing the gene changes behind Alzheimer’s disease have developed a process of making a “meta-cell” that overcomes the challenges of studying a single cell. Their technique has already revealed important new information and can be used to study other diseases throughout the body.

Details about the meta-cell – created by researchers with the UCI Institute for Memory Impairments and Neurological Disorders, known as UCI MIND – were published in the online journal Cell Press.

Technologies called transcriptomics that study sets of RNA within organisms enable scientists to understand what each cell does. However, the question of how particular genes work within a solo cell, a process known as single-cell genomics, has not been widely studied. As a result, it has still been difficult to determine which genes are associated with disease or carrying out normal functions.

“The challenge is that a single cell does not contain much RNA,” said first author Samuel Morabito, a UCI graduate student researcher in the mathematical, computational and systems biology program. “This sparsity makes it hard to study. Even if a gene is present, technology might miss it.”

Sleep apnea link to cognitive decline

Photo Credit: SHVETS production

Flinders University experts are working on better solutions for sleep apnea to ward off a range of health risks, including cognitive decline.

Improved solutions for obstructive sleep apnea (OSA), insomnia and other sleep disorders are being developed by the Flinders Sleep Health experts to reduce the associated negative health effects such as cardiovascular harm, diabetes, anxiety and depression and even long-term cognitive decline.

Heightened risk of cognitive function decline from undiagnosed OSA – particularly in middle-aged men living in the community – is the focus of one of the latest studies published in Sleep Health.

The study recorded the sleep patterns of more than 470 men aged from 41-87 years alongside their daytime cognitive function for processing speed, visual attention, episodic memory recollection and other markers.

Measuring distinct features of brain electrical activity during non-REM sleep, called ‘sleep spindles’, the study aimed to explore if these features can serve as markers of cognitive function.

“Non-REM sleep includes light stage 1 and 2 sleep, as well as deeper stage 3 sleep which is thought to play an important role in learning and memory,” says Flinders University sleep researcher Dr Jesse Parker.

Why women with multiple sclerosis get better when pregnant

Women suffering from the autoimmune disease multiple sclerosis temporarily get much better when pregnant.
Photo Credit: Neal E. Johnson

Women suffering from the autoimmune disease multiple sclerosis temporarily get much better when pregnant. Researchers have now identified the beneficial changes naturally occurring in the immune system during pregnancy. The findings can show the way to new treatments.

Pregnancy is a very special condition from an immunological point of view. The immune system serves to defend us against foreign substances. However, although half of the genetic material of the fetus comes from the father, it is not rejected by the mother’s immune system. One reason why this balancing act is almost always successful is that during pregnancy the mother’s immune system is adapted to become more tolerant.

In multiple sclerosis, MS, nerve function is hampered due to the immune system attacking the fat that serves as an insulating sheath around the nerve fibers. The nerves become inflamed, which could lead to nerve damage. Although new and more effective treatment options are available, most MS patients deteriorate over time.

Researchers believe that the temporary dampening of the immune response could explain why women with MS actually get better when pregnant. Periods of symptoms, i.e. relapses, decrease by 70 percent during the last third of pregnancy. Also, some other autoimmune diseases, such as rheumatoid arthritis, temporarily ameliorate during pregnancy. But the reason for this has not been clear. This is why the researchers behind this study wanted to investigate what mechanisms that could be of particular importance for the decrease in symptoms during pregnancy, as a step to finding future treatment strategies that give the same effect in MS and possibly also other similar diseases.

Our visual perception is more rational than we think

Our visual perception adapts flexibly and unconsciously to the decision context when it’s to our advantage.
Photo Credit: Colin Lloyd

Our visual perception depends more strongly on the utility of information than previously thought. This has been demonstrated in a series of experiments conducted by researchers at the Neuroscience Center Zurich. Cognitive biases can begin at the retina.

Are our senses there to provide us with the most complete representation of the world, or do they serve our survival? For a long time, the former was the dominant view in neuroscience. “Was” is the operative word here. In the last 50 years, psychologists such as Nobel Prize winners Daniel Kahnemann and Amos Tversky have shown that human perception is often anything but complete and instead is highly selective.

Experiments have now verified that there is a whole list of examples of cognitive biases. One of the most important is confirmation bias: we often process new information in a way that confirms our beliefs and expectations.

But up until now, researchers haven’t been able to fully explain under what conditions these distortions come into play and when exactly in the perceptual process they begin. A study by researchers led by University of Zurich Professor Todd Hare and ETH Professor Rafael Polania, recently published in the journal Nature Human Behavior, now shows that the brain already adjusts the visual perception of things on the retina when it is in our interest to do so. Or, to put it another way, we unconsciously see things distorted when it comes to our survival, well-being, or other interests.

Is “second-guessing” a hard-wired behavior? Mouse study offers clues

U of U Health scientists have found that genes bias decision-making, even decisions that seem irrational.
Illustration Credit: Cornelia Stacher-Hörndli, PhD.

Have you ever made a decision that, in hindsight, seemed irrational? A new study with mice, which could have implications for people, suggests that some decisions are, to a certain extent, beyond their control. Rather, the mice are hard-wired to make them.

“This research is telling us that animals are constrained in the decisions they make,” said Christopher Gregg, PhD, a neurobiologist at University of Utah Health and senior author of the study that was recently published in iScience. “Their genetics push them down one path or another.”

Gregg and his research team started investigating decision-making after noticing mice repeatedly making what appeared to be an irrational decision. After finding a stash of hidden seeds, rather than staying put to eat them, mice kept returning to a location that had food in it the day before. Only on this day, the original location was empty.

“It was as if the mice were second-guessing whether the first location really had no food,” Gregg said. “Like they thought they had missed something.”

COVID-19 can cause brain cells to ‘fuse’

Fused neurons in yellow, expressing Spike S fusogen from the SARS-CoV-2 virus and the human receptor hACE2.
Image Credit: Courtesy of University of Queensland

Researchers at The University of Queensland have discovered viruses such as SARS-CoV-2 can cause brain cells to fuse, initiating malfunctions that lead to chronic neurological symptoms.

Professor Massimo Hilliard and Dr Ramon Martinez-Marmol from the Queensland Brain Institute have explored how viruses alter the function of the nervous system.

SARS-CoV-2, the virus that causes COVID-19, has been detected in the brains of people with ‘long COVID’ months after their initial infection.

“We discovered COVID-19 causes neurons to undergo a cell fusion process, which has not been seen before,” Professor Hilliard said.

“After neuronal infection with SARS-CoV-2, the spike S protein becomes present in neurons, and once neurons fuse, they don’t die.”

Newly discovered brain mechanism linked to anxiety, OCD

Distinguished Professor Mario Capecchi, Ph.D. and Naveen Nagajaran, Ph.D.
Photo Credit: Charlie Ehlert/U of U Health

The pandemic and its aftermath have raised anxiety to new levels. But the roots of anxiety-related conditions, including obsessive-compulsive spectrum disorder (OCSD), are still unclear. In a new study, University of Utah Health scientists discovered insights into the importance of a minor cell type in the brain—microglia—in controlling anxiety-related behaviors in laboratory mice. Traditionally, neurons—the predominant brain cell type—are thought to control behavior.

The researchers showed that, like buttons on a game controller, specific microglia populations activate anxiety and OCSD behaviors while others dampen them. Further, microglia communicate with neurons to invoke the behaviors. The findings, published in Molecular Psychiatry, could eventually lead to new approaches for targeted therapies.

“A small amount of anxiety is good,” said Nobel Laureate Mario Capecchi, Ph.D., a distinguished professor of human genetics at the Spencer Fox Eccles School of Medicine at University of Utah and senior author of the study. “Anxiety motivates us, spurs us on, and gives us that extra bit of push that said, ‘I can.’ But a large dose of anxiety overwhelms us. We become mentally paralyzed, the heart beats faster, we sweat, and confusion settles in our minds.”

Progesterone could protect against Parkinson's

Lennart Stegemann (left) and Paula Neufeld are working on their doctoral theses and were able to celebrate an early success with the top-class publication.
Photo Credit: © RUB, Marquard

In one study, progesterone showed a protective effect on the nerve cells of the intestine. This gives hope for the hormone to be used against Parkinson's.

There is mutual communication between the nerve cells of the gastrointestinal tract and those in the brain and spinal cord. It suggests that the digestive nervous system could affect brain processes that lead to Parkinson's. Paula Neufeld and Lennart Stegemann, who are doing their doctorate in the cytology department of the Medical Faculty of the Ruhr University Bochum, have demonstrated progesterone receptors for the first time in the nerve cells of the gastrointestinal tract and have shown that progesterone protects the cells. Their discovery opens up perspectives for the development of novel neuroprotective therapeutic approaches to counteract diseases such as Parkinson's or Alzheimer's. The study is in the journal Cells.

Electrical synapses in the neural network of insects found to have unexpected role in controlling flight power

The fruit fly Drosophila melanogaster flaps its wings two hundred times per second to fly forwards.
 Photo Credit: Silvan Hürke

Researchers of Mainz University and Humboldt-Universität zu Berlin revealed previously unknown function of electrical synapses, thus deciphering the neural circuit used to regulate insect wingbeat frequency

A team of experimental neurobiologists at Johannes Gutenberg University Mainz (JGU) and theoretical biologists at Humboldt-Universität zu Berlin has managed to solve a mystery that has been baffling scientists for decades. They have been able to determine the nature of the electrical activity in the nervous system of insects that controls their flight. In a paper recently published in Nature, they report on a previously unknown function of electrical synapses employed by fruit flies during flight.

The fruit fly Drosophila melanogaster beats its wings around 200 times per second in order to move forward. Other small insects manage even 1,000 wingbeats per second. It is this high frequency of wingbeats that generates the annoying high-pitched buzzing sound we commonly associate with mosquitoes. Every insect has to beat its wings at a certain frequency to not get “stuck” in the air, which acts as a viscous medium due to their small body size. For this purpose, they employ a clever strategy that is widely used in the insect world. This involves reciprocal stretch activation of the antagonistic muscles that raise and depress the wings. The system can oscillate at high frequencies, thus producing the high rate of wingbeats required for propulsion. The motor neurons are unable to keep pace with the speed of the wings so that each neuron generates an electrical pulse that controls the wing muscles only about every 20th wingbeat. These pulses are precisely coordinated with the activity of other neurons. Special activity patterns are generated in the motor neurons that regulate the wingbeat frequency. Each neuron fires at a regular rate but not at the same time as the other neurons. There are fixed intervals between which each of them fires. While it has been known since the 1970s that neural activity patterns of this kind occur in the fruit fly, there was no explanation of the underlying controlling mechanism.

Computational model mimics humans’ ability to predict emotions

While a great deal of research has gone into training computer models to infer someone’s emotional state based on their facial expression, that is not the most important aspect of human emotional intelligence, says MIT Professor Rebecca Saxe. Much more important is the ability to predict someone’s emotional response to events before they occur.
Image Credit: Christine Daniloff, MIT
(CC BY-NC-ND 3.0)

When interacting with another person, you likely spend part of your time trying to anticipate how they will feel about what you’re saying or doing. This task requires a cognitive skill called theory of mind, which helps us to infer other people’s beliefs, desires, intentions, and emotions.

MIT neuroscientists have now designed a computational model that can predict other people’s emotions — including joy, gratitude, confusion, regret, and embarrassment — approximating human observers’ social intelligence. The model was designed to predict the emotions of people involved in a situation based on the prisoner’s dilemma, a classic game theory scenario in which two people must decide whether to cooperate with their partner or betray them. 

To build the model, the researchers incorporated several factors that have been hypothesized to influence people’s emotional reactions, including that person’s desires, their expectations in a particular situation, and whether anyone was watching their actions.

“These are very common, basic intuitions, and what we said is, we can take that very basic grammar and make a model that will learn to predict emotions from those features,” says Rebecca Saxe, the John W. Jarve Professor of Brain and Cognitive Sciences, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the study.

Researchers identify 10 pesticides toxic to neurons involved in Parkinson’s

Photo Credit: Rosyid Arifin

Researchers at UCLA Health and Harvard have identified 10 pesticides that significantly damaged neurons implicated in the development of Parkinson’s disease, providing new clues about environmental toxins’ role in the disease.

While environmental factors such as pesticide exposure have long been linked to Parkinson’s, it has been harder to pinpoint which pesticides may raise risk for the neurodegenerative disorder. Just in California, the nation’s largest agricultural producer and exporter, there are nearly 14,000 pesticide products with over 1,000 active ingredients registered for use.

Through a novel pairing of epidemiology and toxicity screening that leveraged California’s extensive pesticide use database, UCLA and Harvard researchers were able to identify 10 pesticides that were directly toxic to dopaminergic neurons. The neurons play a key role in voluntary movement, and the death of these neurons is a hallmark of Parkinson’s.

Further, the researchers found that co-exposure of pesticides that are typically used in combinations in cotton farming were more toxic than any single pesticide in that group.

New study explains how a common virus can cause multiple sclerosis

Olivia Thomas and Mattias Bronge
Photo Credit: Erik Holmgren

Researchers at Karolinska Institutet have found further evidence for how the Epstein-Barr virus can trigger multiple sclerosis or drive disease progression. A study published in Science Advances shows that some individuals have antibodies against the virus that mistakenly attacks a protein in the brain and spinal cord.

The Epstein-Barr virus (EBV) infects most people early in life and then remains in the body, usually without causing symptoms. The link between EBV and the neurological disease multiple sclerosis (MS) was discovered many years ago and has puzzled researchers ever since. Increasing evidence, including two papers published in Science and Nature last year, suggests that EBV infection precedes MS and that antibodies against the virus may be involved. However, the molecular mechanisms seem to vary between patients and remain largely unknown.

“MS is an incredibly complex disease, but our study provides an important piece in the puzzle and could explain why some people develop the disease,” says Olivia Thomas, postdoctoral researcher at the Department of Clinical Neuroscience, Karolinska Institutet and shared first author of the paper. “We have discovered that certain antibodies against the Epstein-Barr virus, which would normally fight the infection, can mistakenly target the brain and spinal cord and cause damage.”

UC Irvine research team identifies glycosylation enzyme critical in brain formation

Lisa Flanagan, professor of neurology
Photo Credit: Courtesy of University of California, Irvine

The MGAT5 glycosylation enzyme plays a crucial role in brain development, according to a study by University of California, Irvine researchers, a discovery that may contribute to new therapeutic purposes for neural stem cells.

Neurons, astrocytes and oligodendrocytes are the final mature cells of the brain and spinal cord formed by neural stem cells. Each has distinct and key functions. Neurons transmit signals, astrocytes help modify those signals, and oligodendrocytes keep the signals from degrading. When any cells make proteins or fats that end up on the cell surface, they often add small sugar molecules. The team tested whether this internal process – called glycosylation – affects how neural stem cells form mature brain cells.

The study, published in the journal Stem Cell Reports, found that during glycosylation, the MGAT5 enzyme significantly regulates the formation of neurons and astrocytes from neural stem cells. Neural stem cells that don’t have MGAT5 make more neurons and fewer astrocytes during the very early stages of brain development, altering its structure. These changes may contribute to later aberrant behavior patterns, including abnormal social interactions and repetitive actions.

Insight into brain’s waste clearing system may shed light on brain diseases

The image shows a microscopic image revealing the enhanced glymphatic transport of an intranasally delivered tracer (red), achieved using ultrasound combined with microbubbles.
Image Credit: Chen lab

Like the lymphatic system in the body, the glymphatic system in the brain clears metabolic waste and distributes nutrients and other important compounds. Impairments in this system may contribute to brain diseases, such as neurodegenerative diseases and stroke.

A team of researchers in the McKelvey School of Engineering at Washington University in St. Louis has found a noninvasive and nonpharmaceutical method to influence glymphatic transport using focused ultrasound, opening the opportunity to use the method to further study brain diseases and brain function. Results of the work are published in Proceedings of the National Academy of Sciences May 15, 2023.

Hong Chen, associate professor of biomedical engineering in McKelvey Engineering and of neurological surgery in the School of Medicine, and her team, including Dezhuang (Summer) Ye, a postdoctoral research associate, and Si (Stacie) Chen, a former postdoctoral research associate, found the first direct evidence that focused ultrasound, combined with circulating microbubbles — a technique they call FUSMB — could mechanically enhance glymphatic transport in the mouse brain. 

Focused ultrasound can penetrate the scalp and skull to reach the brain and precisely target a defined region within the brain. In previous work, Chen’s team found that microbubbles injected into the bloodstream amplify the effects of the ultrasound waves on the blood vessels and generate a pumping effect, which helps with the accumulation of intranasally-delivered agents in the brain, such as drugs or gene therapy treatments.