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The Nobel Prize Winning Optogenetics Research that Revealed Neuron Mysteries

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From left: Peter Hegemann (Photo: Humboldt University of Berlin/Philipp Plum), Karl Deisseroth (Photo: Christopher Michel/ Wikimedia Commons, CC BY-SA 4.0), Georg Nagel (Photo: Robert Ememrich/University of Würzburg).

Karl Deisseroth, Peter Hegemann and Georg Nagel have been awarded the 2026 Nobel Prize in Physiology or Medicine for their discoveries behind optogenetics, a method that makes it possible to switch nerve cells in the brain on and off using light. The technique has given researchers new tools to understand how specific nerve cells contribute to memories, emotions and behaviour.

Which nerve cells make us feel fear or anxiety? Which ones drive us to move, eat or seek social contact?

The brain consists of billions of nerve cells that are constantly sending electrical signals to one another. For a long time, researchers could observe which nerve cells were active during specific brain processes and behaviours, but they could not determine whether they actually caused the behaviour. Optogenetics changed that.

“There was no way to test what would happen to a behaviour if I activated a particular type of nerve cell or if I stopped the activity of that type of nerve cell? Optogenetics made exactly that possible: to switch the activity of specific nerve cells on or off and observe how the behaviour changed,” says Konstantinos Meletis, professor at the Department of Neuroscience, Karolinska Institutet, who has collaborated with Karl Deisseroth.

The researchers could therefore move from correlation to causality: from observing that a nerve cell is active when a certain behaviour occurs to testing whether the activity in the nerve cell actually causes the behaviour.

“It is so incredibly fundamental, so crucial to brain research. You can divide the history of neuroscience into a ‘before’ and an ‘after’ this discovery. Optogenetics has completely transformed what is possible to do,” says Konstantinos Meletis.

From algae to nerve cells

The story behind this year’s Nobel Prize began in the early 1990s, when the German researcher Peter Hegemann became interested in how the single-celled alga chlamydomonas can detect and swim towards light.

Together with fellow Nobel laureate, George Nagel, also from Germany, he succeeded in identifying a light-sensitive type of protein in the alga during the 2000s. The protein was named channelrhodopsin.

They discovered that when blue light struck the protein, a channel in the cell membrane opened. Electrically charged particles, known as ions, could then flow into the cell and generate an electrical signal. A key finding was that the the same protein and mechanism could also function in other types of cells.

From there came the next major idea.

The American researcher Karl Deisseroth realised that the protein channelrhodopsin could be used to control nerve cells.

The researchers introduced the gene coding for the protein channelrhodopsin into nerve cells grown in a laboratory, leading to formation of the light-sensitive protein on the surface of the nerve cells. When the nerve cells were exposed to blue light, the ion channels opened and the nerve cells began to generate and transmit electrical signals, just as nerve cells naturally do in the brain.

In effect, they had created a light-controlled switch for nerve cells.

Two years later, Karl Deisseroth and his colleagues were able to use the technique to control nerve cells in the brains of living mice.

Since then, optogenetics has become a central tool in neuroscience. By controlling specific nerve cells, researchers can investigate how different brain circuits influence movement, memory, emotions and behaviour.

The technique is also being explored as a potential foundation for future treatments.

“The technology is already being used in attempts to restore vision in people who are blind. The hope is that it will also become a tool for treating neurological disorders such as Parkinson’s disease and Alzheimer’s disease, as well as psychiatric disorders such as depression, anxiety and PTSD,” says Konstantinos Meletis.

A collaboration that spread across the globe

Around 2008, Konstantinos Meletis was a postdoctoral researcher at MIT in the United States alongside Marie Carlén, now a professor at the Department of Neuroscience, Karolinska Institutet. There, they collaborated with Karl Deisseroth’s laboratory at Stanford University. This marked the beginning of a long-standing scientific collaboration. Deisseroth was invited to Karolinska Institutet on several occasions and held an affiliated research position between 2013 and 2019.

“Karl is an absolutely exceptional scientist and human being. In addition to being incredibly intelligent, he is remarkably generous. This has contributed to the breakthrough in optogenetics,” says Marie Carlén, and continues:

“As soon as he set up his lab and carried out the first optogenetics studies in the mid-2000s, he began sharing these tools with others. Since then, they have spread to thousands of laboratories around the world. I would say that is quite unique. It has enabled laboratories everywhere to continue expanding our knowledge of the brain.”

For Konstantinos Meletis, this year’s Nobel Prize is a reminder of the value of basic research and the importance of investing in work whose future significance is not yet known.

“We must be willing to trust the unexpected, to trust major discoveries that arise from things we did not anticipate. Optogenetics did not emerge because someone decided we needed a method to cure a specific disease. It developed frompeople who were deeply committed to a fundamental scientific question. Only later could its potential be recognised,” he says.

He points to Hegemann’s and Nagel’s early research on light-sensitive proteins in algae as an example. At the time, it was far from obvious how important the discovery would become for neuroscience.

“What funding body would choose to support research on algae in order to discover this protein? And yet, 20 years later, it has transformed the entire field of neuroscience. That is what makes it so inspiring.”

Facts about the 2026 Nobel Laureates

Karl Deisseroth

Born in 1971. Received his PhD in 1998 and his medical degree in 2000 from Stanford University,USA. Professor of Biomedical Engineering and of Psychiatry and Behavioural Sciences at the Howard Hughes Medical Institute and Stanford University.

Peter Hegemann

Born in 1954. Received his PhD in 1984 at the Max Planck Institute for Biochemistry in Martinsried, Germany, where the prize-winning discoveries were made. Professor of Neuroscience at Humboldt University in Berlin, Germany.

Georg Nagel

Born in 1953. Received his PhD in 1988 at the University of Frankfurt in Germany. Professor of Molecular Plant Physiology at the University of Würzburg, Germany. The prize-winning discoveries were made at the Max Planck Institute of Biophysics in Frankfurt, Germany.

Text: Anna Björklund

Source: The Nobel Foundation via Karolinska Institutet

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Neurologists Pin Down How Cannabis Causes Anxiety

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For the first time, Northwestern scientists have identified a set of neurons that play a role in generating anxiety after exposure to cannabinoid drugs, especially under stressful conditions. Cannabinoids are a class of substances that includes THC, the main psychoactive ingredient in cannabis.

In the study, the scientists exposed mice to a threatening odor. Before being exposed to the scent, derived from fox urine, the mice either received a placebo or a synthetic cannabinoid drug.

When they received the drug, the mice froze more often and spent less time investigating the predator door. These anxious behaviours, the scientists found, were linked to the drug’s activation of a small group of cells — known as somatostatin neurons — in the brain’s central amygdala, a region that processes fear and stress.

Importantly, when the scientists genetically silenced these somatostatin neurons, the drugged mice did not avoid the predator scent as much anymore.

“The results of this study could explain why a good trip can turn bad pretty quickly if people consume too much cannabis or the situation they are in turns stressful or scary,” said study senior author Dr Sachin Patel, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.  

The study appears in Nature Communications.

How the study was conducted

Patel and colleagues tested several doses of the synthetic cannabinoid on mice and tracked how much time they spent near the predator odor, and whether they froze or fled from the scent. To simultaneously record brain activity, the team implanted a small microscope into the mice’s brain.

The scientists also conducted brain tissue experiments to analyse how the cannabinoids affected interactions between neurons. They found that the drug weakened the brain’s natural “brake” on the somatostatin neurons, allowing them to become more active.

“Higher doses of cannabinoids and environmental stress worked together to synergistically release the ‘brake’ on the central amygdala, which in turn drove excessive anxiety,” Patel explained.

Why the findings matter

Cannabis use in the US has steadily increased in recent years and so have emergency department visits related to adverse effects from the drug. Previous studies have also found an association between cannabis use and increased risk of anxiety in the long term. What’s more, anxiety and mood disorders are also on the rise globally.

“Understanding how cannabis affects brain function to generate its psychoactive effects could ultimately reveal new ways to counteract negative consequences should they arise in some people,” Patel said. 

Patel also noted that the findings could have implications beyond cannabis. “Suppressing the activity of somatostatin neurons in the central amygdala could represent a final pathway for reducing anxiety symptoms, not just in the context of cannabis side effects,” he explained.

Source: Northwestern University via EurakAlert!

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Study Finds Unexpected New Target to Treat Autism Symptoms

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Researchers at The Ottawa Hospital and the University of Ottawa were able to reverse certain behavioural symptoms in a mouse model of autism by fixing a problem in the brain blood vessels. Their findings, published in Neuron, present a promising new treatment target for these symptoms.

Autism is a neurodevelopmental condition with widely varying characteristics. Some of the behavioural symptoms can make life more challenging. While many people with autism have found ways to manage these symptoms, no drug treatment exists. 

“The road from discovery to clinical trials is long, but we’re excited by the possibility that our findings might one day improve the daily lives of people with autism,” said senior author Dr Baptiste Lacoste, senior scientist at The Ottawa Hospital and professor at the University of Ottawa. 

Dr Lacoste’s team previously discovered that blood vessels in the brain don’t work properly in mouse models with a 16p11.2 deletion, one of the most common genetic mutations seen in autism. They were the first to look at what was happening in the blood vessels of the brain. 

The researchers found the problem began in cells lining the blood vessels, called the endothelial cells. These cells make sure blood quickly gets to the parts of the brain that are active. This responsive blood supply is needed for proper brain function. 

However, the endothelial cells in these mice don’t respond quickly enough. This happens early in brain development and causes behavioral symptoms later in life, including hyperactivity, repetitive movements, and motor learning impairment.

In this new study, driven by former PhD student Dr Julie Ouellette, the research team looked at what was wrong with these endothelial cells and whether it could be fixed. 

The team led by Dr Lacoste found that the endothelial cells had half the normal level of a molecule called ATP. ATP is usually considered an energy molecule, but in this case the cell was missing its target, called a P2Y2 receptor, on its surface. 

By activating this P2Y2 receptor, the researchers could restore the cell’s function, increase blood flow in the brain and reverse the behavioral symptoms in adult mice. This was achieved using a drug known to activate P2Y2 and currently approved for humans in Japan and South Korea to treat dry eye syndrome. 

“It’s as if these cells are asleep, and now we can wake them up,” says Dr Lacoste. “And we may only need to treat them once to wake them up permanently. We will test that further, but it’s an encouraging feature for a future treatment.” 

This study only looked at adult mice. This means targeting P2Y2 could reverse behavioural symptoms that were already well established.  Next, the team plans to treat mice earlier in life to see if early treatment has additional benefits. 

The team has also filed a patent application for using P2Y2 activation in the blood vessels to treat autism symptoms. They are interested in exploring drug development with the aim of eventual clinical trials.

Source: University of Ottawa

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Anti-epileptic Drug May Reduce Migraine Aura

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A new study by researchers at Lund University in Sweden found that 85 percent of patients with aura-dominant migraine experienced a reduction in monthly aura days by at least half following treatment with the anti-epileptic drug lamotrigine. The findings need to be confirmed in a controlled study, but could eventually be significant for a patient group that currently lacks a specific treatment for the aura itself.

Around 1.5 million people in Sweden suffer from migraine. Migraine affects both individuals’ daily lives and society as a whole. The disease limits the ability to work and participate in social activities, and leads to significant costs through sick leave, reduced productivity and increased healthcare needs. Women are three times as likely to be affected as often as men, a difference that is largely due to hormonal factors.  

Up to a third of people with migraine experience aura – a temporary neurological symptom that can cause visual disturbances, loss of vision, sensory disturbances, balance problems, and speech and language difficulties, among other symptoms. For some patients, aura is the most debilitating symptom of the disease, but there is currently no established treatment that specifically targets it. 

“Around 50,000 people in Sweden suffer from aura-dominant migraine. Aura is thought to be linked to cortical spreading depolarisation (CSD), a slowly progressing wave of altered nerve cell activity in the cerebral cortex,” says Gürdal Sahin, a researcher at Lund University and a specialist in neurology at the Skåneuro private clinic. 

Migraine with aura is also associated with a slightly increased risk of ischaemic stroke, particularly when combined with other vascular risk factors. It is therefore important to reduce modifiable risk factors. 

“There are now several effective treatments for migraine, including new medicines that block the neurotransmitter CGRP, which plays a key role in migraine attacks. Botulinum toxin is also used as a preventative treatment for chronic migraine. However, as there is no established treatment that specifically targets the aura itself, migraines with and without aura are often treated in a similar way, even though the aura appears to be partly based on mechanisms other than the headache itself,” Gürdal Sahin continues. 

The medicine lamotrigine is approved for the treatment of epilepsy and bipolar disorder, but not for migraine. However, as both epilepsy and migraine aura involve temporary changes in nerve cell activity, the researchers wanted to investigate whether the drug could also prevent aura. Lamotrigine affects the electrical activity of nerve cells by acting on sodium and potassium channels, and also reduces the release of, amongst other things, the neurotransmitter glutamate. In this way, the medicine can reduce the excessive excitability of the nerve cells. In theory, these mechanisms could help to prevent the emergence and spread of CSD. 

“In our study, we examined 81 patients with frequent or particularly troublesome migraine aura and treated them with lamotrigine. Among the patients included the number of days with aura fell on average from 6.9 to 1.4 days per month, representing a reduction of around 80 per cent,” says Sena Uzun, a doctoral student at Lund University. 

While previous studies involving lamotrigine have shown mixed results, the results of this study were particularly promising for patients with aura-dominant migraine. In this group, 85 per cent of patients experienced at least a 50 per cent reduction in the number of days with aura. Another interesting observation was that a slower dose escalation was associated with fewer side effects, which may be relevant when the treatment is evaluated in future clinical trials. 

“As the study is retrospective and lacks a control group, the results need to be confirmed. We are now proceeding with a national, randomised, double-blind, placebo-controlled trial of lamotrigine. If the results can be confirmed, the drug could become a relatively inexpensive and well-established treatment option for a group of patients who currently have no treatment for the aura itself,” concludes Sena Uzun.

Original written by Åsa Hansdotter

Source: Lund University

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Human Brain is Two Separate Organs, New Research Finds

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A new study led by Stanford Medicine found the brain is two separate organs adjacent to one another. The finding could aid research into devastating neurological diseases.

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For centuries, scientists have thought of the brain as a single, unified organ. But new research led by Stanford Medicine reveals that what we call the brain is two distinct organs that evolved independently over hundreds of millions of years.

The discovery overturns a prevailing model of brain development. For decades researchers have subscribed to the theory that there is a single progenitor cell early in development that gives rise to the entire brain. This model suggested all parts of the brain shared a common developmental origin.

The new research finding shows that the human brain consists of two ancient nervous systems cleverly packaged together — a more primitive part that regulates our hearts’ beating, our breathing and other functions, and another that makes us distinctly human, capable of poetry, mathematics and wondering about our own origins.

The discovery could help explain why scientists have struggled for decades to grow certain types of brain cells in the laboratory — and it opens new avenues for studying devastating diseases that affect the brain stem, such as spinal muscular atrophy (also known as SMA) and amyotrophic lateral sclerosis (also known as ALS or Lou Gehrig’s disease).

“We’ve shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain,” said Kyle Loh, PhD, associate professor of developmental biology. “Our discovery means that we can now grow neurons from the back of the brain, the hindbrain, in a petri dish and study their functions.”

The findings were published in Nature Neuroscience Sept. 18. Loh is the senior author. Graduate students Carolyn Dundes and Rayyan Jokhai are co-first authors of the research.

Two brains

The adult brain has three main regions: the forebrain, midbrain and hindbrain. The forebrain handles higher-level thinking — language, consciousness and abstract reasoning. In contrast, the hindbrain, located at the back of the skull and often called the brain stem, controls essential, automatic functions that keep us alive: breathing, sleeping, and regulating our heartbeat and hunger urges. The hindbrain neurons also control the muscles of the face, tongue and throat, which affect speech and swallowing.

Despite the critical importance of the hindbrain, scientists have struggled for decades to generate human hindbrain neurons in the laboratory. This gap has hampered research into devastating diseases affecting the brain stem, including spinal muscular atrophy and amyotrophic lateral sclerosis.

SMA is a leading genetic cause of death in children under 1 year of age. ALS, which is often diagnosed between the ages of 40 and 70, affects both the forebrain and the hindbrain. In both disorders, certain hindbrain neurons gradually cease to function, and the patient loses the ability to swallow, which can cause pneumonia when food or liquid is inhaled into the lungs; eventually, patients lose the ability to breathe.

The researchers’ breakthrough came from studying the earliest moments of embryonic development, during a stage called gastrulation when the body first takes shape. Jokhai and Dundes discovered that the hindbrain follows a separate developmental path, running in parallel to — rather than branching off from — the pathway that creates the forebrain and midbrain.

The researchers learned this from examining developing mouse embryos. They identified two different brain progenitor cells. One, which expresses a gene called Otx2, is destined to become the forebrain and midbrain. The other, which expresses a gene called Gbx2, is committed to forming the hindbrain. They showed that these two cell populations never overlap; they are mutually exclusive from the earliest stages of development.

The team then examined the DNA packaging, or chromatin, in these cells. Chromatin is a way cells determine which genes can be easily accessed and which are bundled away out of reach. What they found was striking: The anterior neural ectoderm (future forebrain and midbrain) and posterior neural ectoderm (future hindbrain) have fundamentally different chromatin configurations. These differences essentially locked each progenitor cell into its respective fate, like travelers on parallel tracks that never cross.

“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” Jokhai said.

This revelation explained decades of frustration in the field — scientists had been trying to turn one type of progenitor cell into another that it is fundamentally incapable of becoming.

“In stem cell biology, people are always fixated with creating the end cell type, like the neuron,” Jokhai said. “But it’s important to begin at the earliest stages of embryonic development. Our careful attention to that early time point allowed us to find this fundamental split in brain development.”

Growing hindbrain neurons

Armed with this knowledge, the researchers for the first time successfully coaxed human pluripotent stem cells (a kind of cell that can create any cell in the human body) to become functional hindbrain motor neurons in the laboratory. These lab-grown neurons displayed all the hallmarks of authentic hindbrain cells: They exhibited waves of electrical activity called action potentials and made proteins that identify the segments of the hindbrain that control facial and swallowing muscles.

Finally, the researchers looked back over 550 million years of evolutionary time. They found the same two-origin brain pattern in chickens; zebrafish; and, remarkably, in acorn worms, tiny creatures living on the ocean floor that share a distant common ancestor with humans. Jellyfish, which diverged from humans about 600 to 700 million years ago, have two nervous systems at different ends of their body.

“Our research suggests that evolution took two existing neural systems and pushed them together spatially,” Loh said. “Having the brain as one organ would probably be more efficient, but we rely on this primordial way to make the brain as two separate pieces.”

“I was surprised at our findings because the word ‘brain’ implies a contiguous organ that likely has a singular origin,” Jokhai said. “But even 500 million years ago, there were these separate neural systems, which now almost operate as one, which is very cool.”

The research also has implications for investigating treatments for SMA, ALS and other conditions affecting the brain stem. Until now, studying these diseases has been nearly impossible because scientists cannot obtain brain stem tissue from living patients. The ability to grow these neurons in a dish opens new possibilities for understanding what goes wrong. There’s even an unexpected connection to obesity treatment: The hindbrain contains circuits that regulate hunger — which is precisely how weight-loss drugs like semaglutide work.

The researchers would like to extend their studies to determine the developmental origins of the spinal cord and to learn exactly how SMA and ALS compromise the function of hindbrain neurons.

“Now we have a model to better understand these devastating diseases, and work toward regenerative therapies for them,” Jokhai said. “This is a very exciting new frontier in brain research.”

Original written by Krista Conger

Source: Stanford Medicine

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Sex Differences in Attention are Present at Birth, Study Finds

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Cambridge scientists have shown that girls and boys show differences in what they pay attention to, even at birth. Since these differences are present so early, it is possible they emerge due to prenatal factors.

It’s nature and nurture, not nature or nurture

Simon Baron-Cohen

The findings suggest that some psychological differences between males and females (such the development of social skills) may be influenced by both prenatal biology as well as later experience.

The study, published today in Biology of Sex Differences, involved testing 130 newborn infants only hours after birth. It builds on previous research by the same lab and uses robust methods to demonstrate the differences.

For years, research has shown that girls, on average, learn to talk earlier and develop social skills faster than boys. Scientists have long debated whether these differences are due to culture or biology. One way to answer this question is to test if sex differences are present soon after birth, before society and culture have influenced a child’s development. 

A study from the University of Cambridge published in 2000 found girls at birth on average looked longer at faces, and boys on average looked longer at objects. Since then, scientists in the field called for a replication of this study. However, no research team has attempted this until now, since it is very challenging to carry out research on newborn infants.   

In this new study, infants were presented with side-by-side videos containing a social stimulus, namely a human face with natural movement, and a non-social object, namely a set of metallic balls swinging due to gravity and their mechanical properties (a Newton’s cradle). 

The team found that, regardless of sex, newborn infants generally preferred to look at the social stimulus. However, on average, female infants spent a greater proportion of the time looking at the social stimulus compared to male infants, while male infants spent a greater proportion of time looking at the non-social stimulus compared to female infants.

Since this is within hours of birth, before much postnatal experience (such as social expectations based on gender) has occurred, it is likely that prenatal biological factors that differ between the sexes during pregnancy (such as hormone levels and genetics) contribute to the observed on-average sex differences. 

Yumnah Khan, a PhD student at the Autism Research Centre, University of Cambridge and the lead researcher on the study, said: “Our recent research has also shown that on-average sex differences are present in brain structure at birth and emerge prenatally. This new study tells us that there are not only on-average sex differences in the brain but also in attention and behaviour.” 

Professor Sir Simon Baron Cohen, Director of the Autism Research Centre, University of Cambridge, who supervised the study, said: “This study addresses the age-old question of whether nature plays any role at all in shaping sex differences in the human mind and brain. The fact that we observe these differences within hours of birth, before extensive postnatal experience has occurred, suggests that prenatal factors play a role, and that these prenatal factors – sex hormones and/or genes – go on to interact with postnatal experience. In other words, it’s nature and nurture, not nature or nurture.”

The new study used more robust methods compared to the original 2000 study. In particular, it included more controlled experimental testing conditions as well as a more reliable method to monitor infant gaze. Crucially, the researchers who analysed the videos of the baby’s eyes were blind to the baby’s sex and whether the baby was looking at the social or the non-social stimulus, which ensured that they could not bias the results. 

Dr Alex Tsompanidis, Assistant Research Professor at the Autism Research Centre and a member of the research team, said: “Sex differences at birth are important as starting points, but we need to remember that they don’t fully determine how children learn and develop in later life. This is because biological and social factors always interact, contributing to the rich diversity of human societies.”

Professor Carrie Allison, Deputy Director of the Autism Research Centre and another member of the research team, said: “The differences we see don’t apply to all male or all female infants, and are only seen when you compare groups of male and female infants, on average. There’s a lot a variation within, and overlap between, each sex. Our future research needs to better understand that variation.” 

The team is now interested to find out if these early sex differences contribute to later differences in children’s minds, brains and behaviour. To test this requires a longitudinal (follow-up) study design, which is underway. The researchers hope that by understanding the origins of the earliest sex differences, scientists can better understand neurodiversity and conditions such as autism, which is diagnosed about twice as often in boys than in girls.

This research was supported by the Wellcome Trust, the Simon Foundation Autism Research Initiative (SFARI), and a PhD studentship from Trinity College, Cambridge and the Cambridge Trust. A follow-up study is funded by the K. Lisa Yang Centre for Autism Research at Cambridge, which is part of the Yang Tan Collective.

Reference

Khan, YT, Tsompanidis, A, Hymanson, E, Wickramanayake, S, APEX Consortium, Austin, T, Allison, C, & Baron-Cohen, S. Sex differences in social attention at birth. Biology of Sex Differences; 21 Sept 2026; DOI: 10.1186/s13293-026-00976-9

Republished from the University of Cambridge under a Creative Commons licence. Read the original article,

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‘Momnesia’ is Real – A Biological Explanation for Temporary Forgetfulness During Pregnancy

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Many women usually say the same thing during pregnancy: they walk into a room and forget why, misplace their keys or struggle to follow a conversation. This phenomenon, often called ‘pregnancy brain’ or ‘momnesia,’ has long lacked a clear biological explanation.

Now, a new study by researchers at Baylor College of Medicine and collaborating institutions and published in Science Bulletin, identifies a specific brain circuit in an animal model that becomes disrupted under the sustained high oestrogen levels present during pregnancy. The findings offer the first biological explanation of how exposure to high-level circulating oestrogen can temporarily impair memory.

A novel brain circuit links high oestrogen levels with memory problems

“We worked with mouse models designed to mimic the sustained, high blood-oestrogen levels of pregnancy. These models showed that elevated oestrogen caused reversible memory impairment without affecting mood or motivation, suggesting a specific cognitive effect rather than a general change in well-being,” said senior author Dr Zheng Sun, associate professor of medicine – endocrinology, diabetes and metabolism and of molecular and cellular biology at Baylor.

Digging into the underlying biology, the team found that oestrogen receptor alpha, the protein that transmits oestrogen’s signals into cells, is the dominant oestrogen receptor in the brain region called the lateral hypothalamus. Furthermore, this region has abundant GABAergic neurons – brain cells that normally send calming, inhibitory signals to other parts of the brain. Using single-nucleus RNA sequencing, the researchers discovered that high oestrogen levels suppress signaling in these neurons, leading them to fire more frequently. “When we genetically removed oestrogen receptors from these hypothalamic neurons, both oestrogen-induced and pregnancy-induced memory problems in mice were reversed,” said Sun, a member of Baylor’s Dan L Duncan Comprehensive Cancer Center.

The team also found that these overactive hypothalamic neurons project directly into a region of the hippocampus that is a hub for memory formation. Using chemogenetics, a technique that allows researchers to turn specific neurons on or off, the team showed that silencing this hypothalamus-to-hippocampus pathway protected mice from estrogen-induced memory problems, whereas artificially activating the same pathway was sufficient to impair memory on its own, even without elevated estrogen.

Reconciling mixed evidence

Oestrogen’s relationship with memory has puzzled researchers for decades. For instance, hormone replacement therapy after menopause has been linked to cognitive benefits in some studies, while high oestrogen during pregnancy or with oral contraceptive use has been linked to memory complaints in others. The new findings suggest a possible explanation – it may not simply be a matter of ‘more oestrogen is better’ or ‘worse,’ but rather where in the brain that oestrogen acts, and at what levels.

“Low-level, cyclical oestrogen exposure appears to support cognitive function, which is part of why hormone therapy can help postmenopausal women,” said senior author Dr Yanlin He, associate professor at Pennington Biomedical Research Center. “But sustained, high-level oestrogen exposure seems to engage a different pathway altogether, one centred in the hypothalamus rather than the hippocampus itself. That distinction may help reconcile a lot of conflicting data in the field.”

Confirming the link in pregnant women

To determine whether these findings translate to humans, the researchers assessed memory performance in women across different stages of pregnancy. They found task-specific memory impairments that emerged during late pregnancy, and that correlated with circulating oestrogen levels, even after accounting for other factors that might influence cognition. This human data supports the idea that the hormone-driven circuit identified in mice may underlie the memory changes many pregnant women experience.

“Momnesia is real, it has a defined biological basis and is temporary,” said senior author Dr Xianghua Zhuang, professor at the Second Qilu Hospital of Shandong University. “We hope this work helps validate what many women have described anecdotally for years, and gives researchers a concrete target for future study.”

“The memory changes observed in both mice and women were temporary and task-specific, not a sign of broader cognitive decline,” said senior author Dr Xinguo Hou, professor at the Qilu Hospital of Shandong University. “Nonetheless, understanding the underlying circuit could eventually inform how clinicians counsel patients about the cognitive side effects of pregnancy or hormonal contraceptives, and could open avenues for therapies targeting this specific pathway without disrupting oestrogen’s broader, beneficial roles in the body.”

Source: Baylor College of Medicine, EurekAlert!

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Trial Testing Out-of-Body Experiences Produces Unexpected Twist

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A test to determine if people who report out-of-body experiences could identify objects in another room produced results no better than chance, but afterward something strange happened: Two participants described, unprompted, researchers’ locations and activities behind closed doors.

The participants’ unexpected observations were not part of the trial’s predefined outcome measures and therefore can’t be considered evidence for out-of-body experiences, or OBEs, UVA Health investigators say. But the unexplained results may help researchers design better, more effective ways to evaluate the potential validity of a phenomenon that has been reported for decades.

“I hope this study encourages researchers to think creatively about how we test these experiences. The unexpected findings give us a potentially useful new direction, but they also need to be tested prospectively and under rigorous conditions before we can know what they mean,” said researcher Marina Weiler, PhD, of the University of Virginia School of Medicine’s Division of Perceptual Studies. “For me, the most important takeaway is that unexpected findings can sometimes help us ask better questions. We now have a specific idea that can be tested in future experiments, and that is exactly what science should do.”

Understanding Out-of-Body Experiences

In the recent trial, conducted in Brazil, 21 participants attempted to identify a random object on a laptop screen in another room. Of the 21, 10 reported having an out-of-body experience, and 13 provided target descriptions. (The 13 included participants who had not reported leaving their bodies but said they could see images on an internal “mental screen” or the like.)

The descriptions the participants gave of the objects on the laptop screen did not prove statistically more accurate than what could be expected from guessing. But during interviews afterward, one participant described how a researcher in another room, behind closed doors, had been seated on the left looking at a laptop screen while another researcher was farther back reading a book. Another participant described how a researcher had been seated on the right, taking notes, while a second was sitting on the left at the computer.

Trial records confirmed both descriptions were correct at the time of the participants’ sessions. Further, there was no way the participants could have seen the researchers, according to the trial organizers.

That has prompted Weiler and her collaborators to propose that the targets provided during OBE trials may play important roles in determining outcomes. It’s possible, they suggest, that memorable, distinctive or emotionally engaging targets may be easier for participants to visualise. Researchers conducting future trials may want to supplement the traditional targets with other unseen details that participants might notice, such as having a researcher wear a distinctive or colorful item of clothing while behind closed doors. 

If participants could recall such items without seeing or being told about them, that might bolster the case for out-of-body remote viewing.

“I hope these findings encourage us to think more deeply about what they might mean for our understanding of consciousness and, ultimately, the nature of reality. If studies demonstrate that people can obtain accurate information that they could not have accessed through their ordinary senses, we would have to reconsider some of our assumptions about the relationship between consciousness, perception and the physical world,” Weiler said. “At its deepest level, this research is not only asking whether out-of-body experiences are real. It is asking what we mean by ‘real’ in the first place, and whether our current understanding of reality is broad enough to account for everything human consciousness can experience.”

Findings Published

The researchers have published their findings in the peer-reviewed journal Explore. The research team consisted of Weiler, Damon Abraham, David J.P. Acunzo and Niffe Hermansson. The researchers have no financial interest in the work.

Source: University of Virginia Health

Categories : NeurologyTags :

Why Some Stroke Patients Fare Better than Others

On By ModernMedia
Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

A clot forms. Blood flow to the brain is blocked. Starved of oxygen, neurons begin to die.

This scenario, known as an ischaemic stroke, plays out in roughly 21 000 people worldwide each day, threatening long-term disability or even death. In recent years, clot-busting drugs and mechanical tools for removing them have revolutionised care.

Yet, even with the clot gone and the vessel clear, up to 50% of patients never recover neurologically. New research from CU Boulder and the University of Antwerp helps explain why.

The study, published in the journal PNAS, reveals in unprecedented detail how the brain’s own defence mechanisms against stroke can backfire, triggering additional micro-clots in minor vessels which can damage tissue long after the primary culprit is gone. 

“We now have a way to explain why so many of these patients are not seeing neurological improvements,” said co-author Debanjan Mukherjee, an assistant professor of mechanical engineering at CU Boulder. “Our findings also point to a new potential target for therapeutics that could be extremely impactful for stroke patients.”

The mystery behind ‘no reflow’

Doctors have long known that removing a stroke-causing clot cannot always restore full blood flow to the brain. But why this phenomenon, known as “no reflow,” occurs has remained a mystery.

To unravel it, Mukherjee, who studies the physics of blood flow, teamed up with senior author Frederik Denorme, an assistant professor of biology at the University of Antwerp who studies, as he puts it, “life after the clot.”

“The dogma used to be that you just need to get rid of that blood clot and then all problems should be solved,” said Denorme. “We now know that is not the case.”

In fact, only about 1 in 10 surviving stroke patients recover completely after a stroke; 25% have minor impairments; and half have moderate to severe impairments.

To examine what, precisely, goes on in the brain after a clot is removed, the research team first turned to mice. 

Using a technique called intravital microscopy, they observed in real time how blood flowed in the brain, and cells behaved, in the hour after mice suffering from stroke underwent endovascular thrombectomy. The procedure involves threading a tool through a blood vessel to pluck out an obstructive clot.

While blood quickly started flowing again post-procedure, the researchers were stunned to see that in many mice, it flowed haphazardly, in fits and starts, even reversing course at certain points.

“We saw it with our own eyes. Blood that was flowing left all of a sudden flowed right and vice versa,” said Denorme. “It was remarkable.”

A Jekyll and Hyde protein

An even closer look revealed that, as the brain tried to divert blood around the original obstruction, tiny clots formed where the haphazard channels converged.

To drill down on why those clots formed, Mukherjee’s FLOWLab recreated this scenario using computer simulations. In other research, his lab has recreated similar scenarios using a 3D artificial brain filled with fake blood. 

These experiments implicated von Willebrand factor—a protein best known for stopping bleeding when we get a cut.

In its resting state, Mukherjee explained, von Willebrand factor is coiled up like a ball of string inside blood vessels, waiting for distress signals from the body that make it stretch out and start forming clots to stop bleeding.

In a brain experiencing a stroke, something else unfolds the ball.

“If there is some kind of fluid motion induced after the clot is removed, it can stretch out that ball into an extended thread that attracts platelets, forms new clots and blocks flow even after the original culprit clot is gone,” Mukherjee said.

Meanwhile, the study showed, the brain’s inflammatory response to stress interferes with safeguards that normally keep the protein’s clotting efforts in check, creating what the authors call “a perfect storm” of collateral damage.

Other experiments, looking at blood from stroke patients at the University of Washington in St. Louis, suggest a similar phenomenon happens in humans too.

“We are the first to really show in this hyperacute phase of stroke what is happening with these cells inside blood vessels,” said Denorme. 

More research is necessary to determine why no reflow happens in some stroke patients but not others. But the study did find that stroke patients with higher blood levels of a pro-inflammatory compound called Interleukin 6 had more overactive von Willebrand factor and fared worse long-term.

The researchers envision a day when therapeutics targeting von Willebrand factor, or the inflammatory compounds that exacerbate its clotting capabilities, could be given to stroke patients alongside clot-busting drugs and surgery.

Notably, several such drugs already exist and are approved for use for other disorders.

“It’s early days. But now that we have a lead on what drives these micro-clots, we have a promising new avenue to explore for improving recovery,” said Denorme.

Original written by Lisa Marshall

Source: University of Colorado Boulder

Categories : Implants and Prostheses NeurologyTags :

Can Total Joint Replacement Particles Reach the Brain?

On By ModernMedia

A study shows they do – but without causing cognitive decline

Photo by Anna Shvets

Total joint replacement is a proven treatment to relieve chronic knee pain, but there have been concerns raised that particles from the device may migrate to the brain and cause memory problems. New research from Rush University shows that may not be a worry.

In a study published by Acta Biomaterialia, researchers found that particles in some people with total joint replacements travelled to the brain but did not cause cognitive decline.

Researchers did find an association of cobalt, a key element of most implants, with more Alzheimer’s disease pathology in the brain.

The particles, called wear debris, are caused by friction and movement in the joint, or, in some cases, corrosion. The newer materials used in joint replacements today make this less likely to occur.

“Implants have a very specific combination of metals such as cobalt, and when they show up together in one particle in the brain in the exact same composition that the implant is, we know it can’t come from any other source,” said Robin Pourzal, PhD, associate professor and director of implant materials analysis.

“For years, we’ve known that particles can deposit in tissues surrounding the joint, but this is the first study to look at the particles deposited in the brain.”

In working with Puja Agarwal, PhD, in the Rush Alzheimer’s Disease Center, the team took a closer look at what was happening cognitively in this group of people

The study included data collected among 701 deceased participants in the ongoing Memory and Aging Project conducted by David Bennett, MD, which include older adults residing in the greater Chicago area. The participants had no dementia at the beginning of the study and were followed annually with cognitive assessments using a 19-test battery, a standard collection of memory and thinking skill tests.

A total of 229 people in the study had a total hip, knee or shoulder replacement. The control group was made up of 472 people who had no total joint replacement. Due to a higher likelihood of the metal cobalt being found in total hip replacement, the participants were studied in two groups: 146 with hip replacements and 83 with knee or shoulder replacements. 

Pourzal notes that the collaboration was led by faculty members from the Department of Orthopedic Surgery, including leaders from Rush Orthopedic Research, in collaboration with colleagues from the Rush Alzheimer’s Disease Center and international partners.

“Total joint arthroplasty remains one of the most successful and life-changing interventions in modern medicine. But it does suggest that wear particles from the implant, particularly in certain hip replacements involving accelerated wear, may travel beyond the joint and warrant further study.”

Source: Rush University Medical Center