Category Archives: Neuroscience

Neuroscience

Pregnancy’s Toll: Accelerated Aging in Young Mothers – Neuroscience News

Summary: Pregnancy may accelerate biological aging in women. Utilizing advanced epigenetic clocks to measure DNA methylation, researchers compared the biological age of women with varying numbers of pregnancies against those who had never been pregnant, revealing that increased pregnancies correlate with signs of accelerated aging.

This effect was not observed in men, suggesting a unique biological cost associated with pregnancy and possibly breastfeeding. The findings, which highlight a significant gap in our understanding of the reproductive costs on womens health, point to the urgent need for supportive measures for young mothers, especially in contexts of limited resources.

Key Facts:

Source: Columbia University

Pregnancy may carry a cost, reports a new study from the Columbia University Mailman School of Public Health.

The research, carried out among 1735 young people in the Philippines, shows that women who reported having been pregnant looked biologically older than women who had never been pregnant, and women who had been pregnant more often looked biologically older than those who reported fewer pregnancies.

Notably, the number of pregnancies fathered was not associated with biological aging among same-aged cohort men, which implies that it is something about pregnancy or breastfeeding specifically that accelerates biological aging.

The findings are published inThe Proceedings of National Academy of Sciences.

This study builds on epidemiological findings that high fertility can have negative side effects on womens health and longevity. What was unknown, however, was whether the costs of reproduction were present earlier in life, before disease and age-related decline start to become apparent.

Until now, one of the challenges has been quantifying biological aging among the young. This challenge was overcome by using a collection of new tools that use DNA methylation (DNAm) to study different facets of cellular aging, health, and mortality risk. These tools, called epigenetic clocks allow researchers to study aging earlier in life, filling a key gap in the study of biological aging.

Epigenetic clocks have revolutionized how we study biological aging across the lifecourse and open up new opportunities to study how and when long-term health costs of reproduction and other life events take hold, said Calen Ryan PhD, lead author of the study and associate research scientist in the Columbia Aging Center.

Our findings suggest that pregnancy speeds up biological aging, and that these effects are apparent in young, high-fertility women, said Ryan.

Our results are also the first to follow the same women through time, linking changes in each womans pregnancy number to changes in her biological age.

The relationship between pregnancy history and biological age persisted even after taking into account various other factors tied to biological aging, such as socioeconomic status, smoking, and genetic variation, but were not present among men from the same sample.

This finding, noted Ryan, points to some aspect of bearing children rather than sociocultural factors associated with early fertility or sexual activity as a driver of biological aging.

Despite the striking nature of the findings, Ryan encourages readers to remember the context: Many of the reported pregnancies in our baseline measure occurred during late adolescence, when women are still growing.

We expect this kind of pregnancy to be particularly challenging for a growing mother, especially if her access to healthcare, resources, or other forms of support is limited.

Ryan also acknowledged that there is more work to do, We still have a lot to learn about the role of pregnancy and other aspects of reproduction in the aging process. We also do not know the extent to which accelerated epigenetic aging in these particular individuals will manifest as poor health or mortality decades later in life.

Ryan said that our current understanding of epigenetic clocks and how they predict health and mortality comes largely from North America and Europe, but that the aging process can take slightly different forms in the Philippines and other places around the world.

Ultimately I think our findings highlight the potential long-term impacts of pregnancy on womens health, and the importance of taking care of new parents, especially young mothers.

Co-authors are Christopher Kuzawa, Northwestern University, Nanette R. Lee and Delia B. Carba,USC-Office of Population Studies Foundation; Julie L. MacIsaac, David S. Lin, and Parmida Atashzay, University of British Columbia; Daniel BelskyColumbia Public Health and Columbia Aging Center; Michael S. Kobor, University of British Columbia, Canadian Institute for Advanced Research, Centre for Molecular Medicine and Therapeutics.

Funding: The study was supported by the National Institutes of Health R01AG061006; National Science Foundation BCS 1751912; University of British Columbia UBC 60055724

Author: Stephanie Berger Source: Columbia University Contact: Stephanie Berger Columbia University Image: The image is credited to Neuroscience News

Original Research: The findings will appear in PNAS

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Pregnancy's Toll: Accelerated Aging in Young Mothers - Neuroscience News

Neuroscience

Learning and Memory Formation’s Molecular Basis – Neuroscience News

Summary: Researchers developed a new platform to explore dendritic translations role in memory formation and its implications for intellectual disorders. By employing a novel method named TurboID, researchers uncovered a suite of previously unknown factors involved in memory-related protein synthesis within dendrites, shedding light on the molecular mechanisms that could underlie conditions like Fragile X syndrome.

This study marks a significant advance in understanding how protein synthesis in dendrites contributes to learning and memory, potentially opening new pathways for treating neurodevelopmental disorders. The teams findings suggest that the localized production of proteins, including newly discovered micropeptides, within dendrites is crucial for memory formation, with implications for diseases characterized by memory impairment.

Key Facts:

Source: Rockefeller University

Less than twenty minutes after finishing this article, your brain will begin to store the information that youve just read in a coordinated burst of neuronal activity.

Underpinning this process is a phenomenon known as dendritic translation, which involves an uptick in localized protein production within dendrites, the spiny branches that project off the neuron cell body and receive signals from other neurons at synapses. Its a process key to memoryand its dysfunction is linked to intellectual disorders.

That makes the inner workings of dendritic translation a holy grail for understanding memory formation, says RockefellersRobert B. Darnell, whose team just publisheda study inNature Neurosciencedescribing a new platform capable of identifying the specific regulatory mechanisms that drive dendritic translation.

The team leveraged a method, dubbed TurboID, to discover an entire suite of previously unknown factors in memory formation, revealing now mechanisms that underlie how protein synthesis in dendrites contributes to learning and memory.

The findings may also have implications for intellectual disabilities, such as Fragile X syndrome.

Technological limitations have long prevented a comprehensive inventory of the activity at the synapse involved in memory formation, says lead author Ezgi Hacisuleyman, who conducted the research as a postdoctoral researcher in Darnells laboratory. She is now an assistant professor at The UF Scripps Institute.

Our new techniques can accomplish this with extremely high resolution to look at neurons in vitro that are closely mimicking what we see in the brain.

Hacisuleymans work defines a whole new biochemical pathway which fits with, complements, and vastly expands what we already knew about memory and learning, adds Darnell, the Robert and Harriet Heilbrunn professor.

A unique way to metabolize RNA

Memory formation centers around the hippocampus, a brain region so central to learning that, when surgeons removed it from people with epilepsy in the 1940s, the patients remembered their childhoods but lost the ability to form new memories.

It has since become clear that memories form, in part, because of new protein synthesis made locally in the dendrites of the hippocampus.

Darnell, a physician-scientist, observed the importance of dendritic translation firsthand while working with patients whose immune systems had attacked the hippocampus.

I would talk to a patient for 30 minutes, leave the room, walk back in, and it was like they had never seen me before, he says.

Thats when I began focusing on why neurons of the hippocampus have their own system for regulating RNA metabolisma system that no other cell in the body uses.

That system, it turns out, lies at the heart of how our brains form memories and learn new information, and became a focus for the Darnell lab, culminating in his teams 2003 development of CLIP, a method that allowed researchers to study the proteins that bind and influence RNA. But limitations remained.

Many details about how neurons respond to stimuli at the dendrites were still missing, Hacisuleyman says.

We needed that information, because that plays a role in determining how neurons functionand where things often go awry in neurologic disease.

1,000 micropeptides

To get a better idea of the role that changes in dendrites play in learning, Hacisuleyman extended the TurboID platform to works in concert with RNA-sequencing, CLIP, translation and protein analysis.

The platform allowed the team to track activity in dendrites before, during, and several minutes after the neuron activates, capturing the moments critical to protein synthesis in the cell and, more importantly, the stage considered key to memory formation.

An analysis of these crucial moments revealed a microscopic upheaval in the dendrite. Upon activation, local ribosomes jump onto mRNAs, an action that has all the biochemical hallmarks of memory formation, and which models predicted will cause the dendrite to produce not only new proteins, but 1,000 small proteins known as micropeptides, with as-yet unknown function.

The team also identified an RNA-binding protein that helps seal the connection between these ribosomes and mRNA, and demonstrated that if that protein is disabled, the proposed micropeptides will not form.

We never knew these micropeptides might even exist, Darnell says.

It opens a new field of study, where we can ask what these peptides might be doing and how they could play into memory formation. Its such a vast discovery that there are dozens if not hundreds of avenues in which to pursue this.

Among the many observations that researchers will unpack in future studies, one stood out: the team noted that a certain protein stood out for its prolific binding of mRNA in the dendrite.

The protein, called FMRP, is key to brain development and function, and genetic mutations that adversely impact FMRP contribute to Fragile X syndrome, one of the most common genetic causes of intellectual disability.

Our findings fit nicely with the molecular biology of FMRP, and also open the door to future insights into what is going wrong in Fragile X, Darnell says.

Beyond the papers immediate findings, dendritic-TurboID could also allow researchers to examine protein synthesis in other brain regions and apply the findings to different diseases.

We can now begin to look at many other sites with a fine-toothed comb, Hacisuleyman says.

When you develop a new technique as Hacisuleyman did, you enter a room that nobody has ever been in before, Darnell adds. The light turns on, and the findings just take your breath away.

Author: Katherine Fenz Source: Rockefeller University Contact: Katherine Fenz Rockefeller University Image: The image is credited to Neuroscience News

Original Research: Open access. Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding by Robert B. Darnell et al. Nature Neuroscience

Abstract

Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding

Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear.

In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry.

Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated.

For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism.

This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control.

These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.

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Learning and Memory Formation's Molecular Basis - Neuroscience News

Neuroscience

Acetaminophen in Pregnancy Not Linked to Autism, ADHD Risk – Neuroscience News

Summary: A comprehensive study involving over 2.4 million Swedish children has debunked the notion that acetaminophen use during pregnancy increases the risk of autism, ADHD, and intellectual disability in offspring. The research employed a novel sibling comparison method to eliminate confounding familial and environmental factors, revealing no increased risk of neurodevelopmental disorders among siblings exposed to acetaminophen prenatally versus those who were not.

This finding challenges previous reports linking acetaminophen with such risks and offers reassurance to expectant parents regarding the safety of this common pain reliever during pregnancy.

Key Facts:

Source: Drexel University

In the largest study to date on the subject, researchers found no evidence to support a causal link between acetaminophen use during pregnancy and increased risk of autism, ADHD and intellectual disability in children.

The findings, using data from a nationwide cohort of over 2.4 million children born in Sweden, including siblings not exposed to the drug before birth, were published today in the Journal of theAmerican Medical Association(JAMA) from researchers atDrexels Dornsife School of Public HealthandKarolinska Institutetof Sweden.

Advertised as a pain reliever and fever reducer, the generic drug acetaminophen is the active ingredient in Tylenol and is an ingredient in versions of other drugs, such as Theraflu, Excedrin, and Mucinex, among others.

Following each child up to 26 years after birth, the team found a small increased risk of autism, ADHD and intellectual disability in the overall population as seen in similar previous studies that reported such a link.

However, the authors found no increased risk of any of the conditions when comparing full siblings when one sibling was exposed to acetaminophen while in the uterus before birth and the other sibling was not.

Because siblings share a substantial portion of their genetic background, as well as similar exposure to many of the same environmental factors during development, comparing siblings helps to control for these shared factors that are otherwise hard to measure in epidemiological studies, the authors noted.

Users of acetaminophen differ from non-users in a number of ways and standard statistical analyses without a sibling control cant control for all of the differences, said co-senior authorBrian Lee, PhD, an associate professor in DrexelsDornsife School of Public Health, fellow at theA.J. Drexel Autism Institute, and research affiliate at the Karolinska Institutet.

Sibling comparisons allow us to control for familial characteristics that might explain an apparent relationship between acetaminophen use during pregnancy and risk of neurodevelopmental conditions.

Using data from Swedens national health and prescription drug registers, the researchers gathered data on medication use throughout pregnancy for births from 1995 to 2019.

Only about 7.5% of the study sample 185,909 children were exposed to acetaminophen during pregnancy. In previous studies, acetaminophen use during pregnancy varied greatly depending on the study setting; astudyin Denmark reported 6.2% use while onestudyin the U.S. reported 10-fold higher use.

Previous studies suggested that many pregnant people, who may benefit from acetaminophen, do not take it for fear of side effects, such as a2019 studythat surveyed 850 pregnant Swedish persons, in which more than 60% considered medication use during early pregnancy to be probably harmful or harmful.

This studys findings may be welcome news for birthing people who use acetaminophen as a pain or fever management option, since there are few safe alternatives for relief available, said co-senior authorRenee M. Gardner, PhD, of Swedens Karolinska Institutet.

We hope that our results provide reassurance to expectant parents when faced with the sometimes fraught decision of whether to take these medications during pregnancy when suffering from pain or fever.

The authors say all patients should follow the guidance from their physician on whether acetaminophen is safe for them and their future children.

The study authors said that the statistically increased risk of neurodevelopmental disorders in children exposed to acetaminophen in the womb is likely due to other factors.

Our study and others suggest there are many different health and familial factors that are associated with both acetaminophen use and neurodevelopmental disorders, said Lee. Genetics likely play a role, but future work to elucidate this mechanism is crucial.

In 2015, theU.S. Food and Drug Administrationsaid that studies on over-the-counter pain medicines are too limited to make any recommendations, but noted that severe and persistent pain that is not effectively treated during pregnancy can result in depression, anxiety, and high blood pressure in the mother.

A 2021consensus statement inNature Reviews Endocrinologyby an international group of scientists and clinicians recommended that pregnant individuals minimize exposure (to acetaminophen) by using the lowest effective dose for the shortest possible time due to research suggesting that prenatal exposure to the drug could increase the risk of neurodevelopmental and other disorders.

Although the Drexel and Karolinskastudy used data on prescribed acetaminophen and reports from pregnant people to their midwives during prenatal care and may not capture all over-the-counter use in all patients, the findings represent data from a large representative sample and controls for many other factors that may be linked to neurodevelopmental disorders.

Funding: The study was supported by National Institutes of Healths National Institute of Neurological Disorders and Stroke 1R01NS107607. Beyond funding, NIH had no role in carrying out the study or interpretation of its findings. Lee has received consulting fees for literature reviews for law firms, but has provided no expert litigation, and no external parties had any role in the study.

Other than Gardner and Lee, other authors on the paper include shared lead authors Viktor H. Ahlqvist, PhD, and Hugo Sjqvist, Christina Dalman, MD, PhD, Hkan Karlsson, PhD, Olof Stephansson, MD, PhD, Stefan Johansson, MD, PhD, and Cecilia Magnusson, MD, PhD, all who hold academic appointments at the Karolinska Institutet.

Author: Greg Richter Source: Drexel University Contact: Greg Richter Drexel University Image: The image is credited to Neuroscience News

Original Research: The findings will appear in JAMA

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Acetaminophen in Pregnancy Not Linked to Autism, ADHD Risk - Neuroscience News

Neuroscience

Childhood Loneliness Linked to Later Psychosis – Neuroscience News

Summary: Childhood loneliness significantly increases the likelihood of experiencing a psychotic episode later in life, particularly in women. Through an observational case-control study involving 285 first-episode psychosis patients and 261 controls, the research distinguished the effects of subjective loneliness from objective social isolation.

Key findings demonstrate that loneliness before age 12 doubles the risk of psychosis, with a notably stronger correlation in women. These insights emphasize the importance of early interventions targeting social connectedness to mitigate the risk of developing psychotic disorders.

Key Facts:

Source: European Psychiatric Association

A new study suggests that children who felt lonely for more than 6 months before the age of 12 are more likely to experience an episode of psychosis than children who did not, with women more affected than men.

Psychosis refers to a collection of symptoms that affect a persons mind, where there has been some loss of contact with reality.During an episode of psychosis, a person may have difficulty recognising what is real and what is not.

Symptoms of psychosis include hallucinations, delusions and confused thoughts.In some instances, psychosis may be a symptom of other mental health conditions, such as schizophrenia, bipolar disorder, or severe depression.

Symptoms of schizophrenia are often categorised as positive (any change in behaviour or thoughts, such as hallucinations or delusions), negative (where people appear to withdraw from the world around them).

Loneliness is defined as the subjective feeling of distress associated with a lack of meaningful relationships, regardless of the amount of social contact, whereas social isolation is defined as the objective lack of social contact or support.

In an observational, case-control study, researchers assessed loneliness in children with the question Have you ever felt lonely for more than 6 months before the age of 12 and differentiated this from social isolation by using the peer relationships item from the Premorbid Adjustment Scale.

The study sample comprised 285 patients who had experienced their first episode of psychosis and 261 controls.

Key findings from the study include:

Dr Covadonga Daz-Caneja of the Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Maran, Madrid, Spain, saidThere is increasing evidence of the negative health and social consequences of loneliness in adults, but much less is known about the long-term effects of loneliness in young people.

Despite their preliminary nature, our results suggest that childhood loneliness may serve as an early risk factor for later psychotic disorders and support its role as a potential target for preventive mental health interventions from an early age.

This may be especially relevant considering that childhood loneliness is a prevalent phenomenon that appears to be increasing in recent years.

This study offers valuable insight into the association between childhood loneliness and first-episode psychosis. With the rise of digitalisation and social isolation, loneliness has become a pervasive issue affecting young individuals.

The compelling findings of this study, which establish a direct connection between childhood loneliness and the onset of psychosis, highlight a concerning trend and underscore the importance of addressing social connectedness and emotional well-being from an early age,said Professor Andrea Fiorillo, President Elect of the European Psychiatric Association.

Author: Sarah Carter Source: European Psychiatric Association Contact: Sarah Carter European Psychiatric Association Image: The image is credited to Neuroscience News

Original Research: The findings will be presented at the 32nd European Congress of Psychiatry

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Childhood Loneliness Linked to Later Psychosis - Neuroscience News

Neuroscience

Vigil Neuroscience, Inc. (NASDAQ:VIGL) Expected to Post Q1 2024 Earnings of ($0.58) Per Share – Defense World

Vigil Neuroscience, Inc. (NASDAQ:VIGL Free Report) Research analysts at HC Wainwright issued their Q1 2024 earnings per share estimates for shares of Vigil Neuroscience in a research report issued on Wednesday, March 27th. HC Wainwright analyst A. Fein expects that the company will earn ($0.58) per share for the quarter. HC Wainwright has a Buy rating and a $24.00 price objective on the stock. The consensus estimate for Vigil Neurosciences current full-year earnings is ($2.56) per share. HC Wainwright also issued estimates for Vigil Neurosciences Q3 2024 earnings at ($0.58) EPS.

Separately, Morgan Stanley cut Vigil Neuroscience from an equal weight rating to an underweight rating and decreased their price objective for the company from $13.00 to $4.00 in a report on Tuesday, December 19th. One research analyst has rated the stock with a sell rating and four have given a buy rating to the stock. According to data from MarketBeat, the company presently has a consensus rating of Moderate Buy and an average price target of $17.40.

NASDAQ:VIGL opened at $3.41 on Thursday. The stocks fifty day moving average price is $3.06 and its two-hundred day moving average price is $4.32. Vigil Neuroscience has a 52-week low of $2.53 and a 52-week high of $11.11. The company has a market cap of $122.35 million, a price-to-earnings ratio of -1.60 and a beta of 1.80.

Several hedge funds have recently bought and sold shares of the company. Strs Ohio acquired a new stake in Vigil Neuroscience during the fourth quarter worth approximately $27,000. Royal Bank of Canada acquired a new stake in Vigil Neuroscience during the second quarter worth approximately $33,000. California State Teachers Retirement System acquired a new stake in Vigil Neuroscience during the second quarter worth approximately $50,000. Wells Fargo & Company MN lifted its position in Vigil Neuroscience by 6,988.4% during the second quarter. Wells Fargo & Company MN now owns 6,096 shares of the companys stock worth $57,000 after acquiring an additional 6,010 shares during the last quarter. Finally, MetLife Investment Management LLC acquired a new stake in Vigil Neuroscience during the second quarter worth approximately $86,000. 83.64% of the stock is currently owned by institutional investors and hedge funds.

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Vigil Neuroscience, Inc, a clinical-stage biotechnology company, focuses on developing treatments for rare and common neurodegenerative diseases by restoring the vigilance of microglia, the sentinel immune cells of the brain. Its lead candidate is VGL101, a human monoclonal antibody agonist targeting human triggering receptor expressed on myeloid cells 2 and is in a Phase 2 proof-of-concept trial in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare and fatal neurodegenerative disease.

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Vigil Neuroscience, Inc. (NASDAQ:VIGL) Expected to Post Q1 2024 Earnings of ($0.58) Per Share - Defense World

Neuroscience

International Brain Research Organisation (IBRO) Diversity Grants 2024 Opportunity Desk – Opportunity Desk

Deadline: April 15, 2024

Applications are open for the International Brain Research Organisation (IBRO) Diversity Grants 2024. IBROs core values aim to serve the global neuroscience community through the promotion of diversity, equity, and inclusion in neuroscience research. In alignment with this vision, the IBRO Diversity Grants seek to support events that prioritize and foster regional and gender diversity in neuroscience. This program specifically targets neuroscience societies and other event organizers.

Applicants interested in applying to this funding program are encouraged to address the unique needs prevalent in their region and/or country. IBRO acknowledges the fact that cultural, socio-economic and infrastructural contexts shape the practice of neuroscience globally and encourages applicants to craft proposals tailored to address these unique diversity challenges.

Funds will be transferred according to an 80:20 format. This means that 80% of the grant will be awarded two months prior to the start date of the event, whereas the remaining 20% will be processed upon completion of the event and submission of the required grant report.

Grant

Eligibility

Application

Click here to apply

For more information, visit IBRO Diversity Grants.

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International Brain Research Organisation (IBRO) Diversity Grants 2024 Opportunity Desk - Opportunity Desk

Neuroscience

Hereditary Alzheimer’s Transmitted Via Bone Marrow Transplants – Neuroscience News

Summary: Alzheimers disease, traditionally seen as a brain-centric condition, may have systemic origins and can be accelerated through bone marrow transplants from donors with familial Alzheimers to healthy mice.

A new study underscores the diseases potential transmission via cellular therapies and suggests screening donors for Alzheimers markers to prevent inadvertent disease transfer.

By demonstrating that amyloid proteins from peripheral sources can induce Alzheimers in the central nervous system, this research shifts the understanding of Alzheimers towards a more systemic perspective, highlighting the need for cautious screening in transplants and blood transfusions.

Key Facts:

Source: Cell Press

Familial Alzheimers disease can be transferred via bone marrow transplant, researchers show March 28 in the journalStem Cell Reports. When the team transplanted bone marrow stem cells from mice carrying a hereditary version of Alzheimers disease into normal lab mice, the recipients developed Alzheimers diseaseand at an accelerated rate.

The study highlights the role of amyloid that originates outside of the brain in the development of Alzheimers disease, which changes the paradigm of Alzheimers from being a disease that is exclusively produced in the brain to a more systemic disease.

Based on their findings, the researchers say that donors of blood, tissue, organ, and stem cells should be screened for Alzheimers disease to prevent its inadvertent transfer during blood product transfusions and cellular therapies.

This supports the idea that Alzheimers is a systemic disease where amyloids that are expressed outside of the brain contribute to central nervous system pathology, says senior author and immunologist Wilfred Jefferies, of the University of British Columbia.

As we continue to explore this mechanism, Alzheimers disease may be the tip of the iceberg and we need to have far better controls and screening of the donors used in blood, organ and tissue transplants as well as in the transfers of human derived stem cells or blood products.

To test whether a peripheral source of amyloid could contribute to the development of Alzheimers in the brain, the researchers transplanted bone marrow containing stem cells from mice carrying a familial version of the diseasea variant of the human amyloid precursor protein (APP) gene, which, when cleaved, misfolded and aggregated, forms the amyloid plaques that are a hallmark of Alzheimers disease.

They performed transplants into two different strains of recipient mice: APP-knockout mice that lacked an APP gene altogether, and mice that carried a normal APP gene.

In this model of heritable Alzheimers disease, mice usually begin developing plaques at 9 to 10 months of age, and behavioral signs of cognitive decline begin to appear at 11 to 12 months of age. Surprisingly, the transplant recipients began showing symptoms of cognitive decline much earlierat 6 months post-transplant for the APP-knockout mice and at 9 months for the normal mice.

The fact that we could see significant behavioral differences and cognitive decline in the APP-knockouts at 6 months was surprising but also intriguing because it just showed the appearance of the disease that was being accelerated after being transferred, says first author Chaahat Singh of the University of British Columbia.

In mice, signs of cognitive decline present as an absence of normal fear and a loss of short and long-term memory. Both groups of recipient mice also showed clear molecular and cellular hallmarks of Alzheimers disease, including leaky blood-brain barriers and buildup of amyloid in the brain.

Observing the transfer of disease in APP-knockout mice that lacked an APP gene altogether, the team concluded that the mutated gene in the donor cells can cause the disease and observing that recipient animals that carried a normal APP gene are susceptible to the disease suggests that the disease can be transferred to health individuals.

Because the transplanted stem cells were hematopoietic cells, meaning that they could develop into blood and immune cells but not neurons, the researchers demonstration of amyloid in the brains of APP knockout mice shows definitively that Alzheimers disease can result from amyloid that is produced outside of the central nervous system.

Finally the source of the disease in mice is a human APP gene demonstrating the mutated human gene can transfer the disease in a different species.

In future studies, the researchers plan to test whether transplanting tissues from normal mice to mice with familial Alzheimers could mitigate the disease and to test whether the disease is also transferable via other types of transplants or transfusions and to expand the investigation of the transfer of disease between species.

In this study, we examined bone marrow and stem cells transplantation. However, next it will be important to examine if inadvertent transmission of disease takes place during the application of other forms of cellular therapies, as well as to directly examine the transfer of disease from contaminated sources, independent from cellular mechanisms, says Jefferies.

Funding:

This research was supported by the Canadian Institutes of Health Research, the W. Garfield Weston Foundation/Weston Brain Institute, the Centre for Blood Research, the University of British Columbia, the Austrian Academy of Science, and the Sullivan Urology Foundation at Vancouver General Hospital.

Author: Kristopher Benke Source: Cell Reports Contact: Kristopher Benke Cell Reports Image: The image is credited to Neuroscience News

Original Research: The findings will appear in Stem Cell Reports

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Hereditary Alzheimer's Transmitted Via Bone Marrow Transplants - Neuroscience News

Neuroscience

Household Chemicals Linked to Brain Health Risks – Neuroscience News

Summary: Certain household chemicals, including those found in personal-care products and furniture, pose a risk to brain health, potentially contributing to multiple sclerosis and autism. The study reveals that these chemicals damage oligodendrocytes, essential cells for nerve cell protection.

Key findings include the identification of harmful organophosphate flame retardants and quaternary ammonium compounds, with the latter increasing in use since the COVID-19 pandemic. This groundbreaking research suggests a need for further investigation into the impact of these chemicals on neurological diseases and calls for more rigorous scrutiny and regulation to protect public health.

Key Facts:

Source: Case Western Reserve

A team of researchers from theCase Western Reserve University School of Medicinehas provided fresh insight into the dangers some common household chemicals pose to brain health.

They suggest that chemicals found in a wide range of items, from furniture to hair products, may be linked to multiple sclerosis and autism spectrum disorders.

Neurological problems impact millions of people, but only a fraction of cases can be attributed to genetics alone, indicating that unknown environmental factors are important contributors to neurological disease.

The new study published today in the journalNature Neuroscience, discovered that some common home chemicals specifically affect the brains oligodendrocytes, a specialized cell type that generates the protective insulation around nerve cells.

Loss of oligodendrocytes underlies multiple sclerosis and other neurological diseases,said the studys principal investigator,Paul Tesar,the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and director of the Institute for Glial Sciences at the School of Medicine.

We now show that specific chemicals in consumer products can directly harm oligodendrocytes, representing a previously unrecognized risk factor for neurological disease.

On the premise that not enough thorough research has been done on the impact of chemicals on brain health, the researchers analyzed over 1,800 chemicals that may be exposed to humans.

They identified chemicals that selectively damaged oligodendrocytes belong to two classes: organophosphate flame retardants and quaternary ammonium compounds.

Since quaternary ammonium compounds are present in many personal-care products and disinfectants, which are being used more frequently since the COVID-19 pandemic began, humans are regularly exposed to these chemicals. And many electronics and furniture include organophosphate flame retardants.

The researchers used cellular and organoid systems in the laboratory to show that quaternary ammonium compounds cause oligodendrocytes to die, while organophosphate flame retardants prevented the maturation of oligodendrocytes.

They demonstrated how the same chemicals damage oligodendrocytes in the developing brains of mice. The researchers also linked exposure to one of the chemicals to poor neurological outcomes in children nationally.

We found that oligodendrocytesbut not other brain cellsare surprisingly vulnerable to quaternary ammonium compounds and organophosphate flame retardants, saidErin Cohn, lead author and graduate student in the School of MedicinesMedical Scientist Training Program.

Understanding human exposure to these chemicals may help explain a missing link in how some neurological diseases arise.

The association between human exposure to these chemicals and effects on brain health requires further investigation, the experts warned. Future research must track the chemical levels in the brains of adults and children to determine the amount and length of exposure needed to cause or worsen disease.

Our findings suggest that more comprehensive scrutiny of the impacts of these common household chemicals on brain health is necessary, Tesar said.

We hope our work will contribute to informed decisions regarding regulatory measures or behavioral interventions to minimize chemical exposure and protect human health.

Additional contributing researchers from Case Western Reserve School of Medicine and from theU.S. Environmental Protection Agencyincluded Benjamin Clayton, Mayur Madhavan, Kristin Lee, Sara Yacoub, Yuriy Fedorov, Marissa Scavuzzo, Katie Paul Friedman and Timothy Shafer.

The research was supported by grants from theNational Institutes of Health,National Multiple Sclerosis Society,Howard Hughes Medical InstituteandNew York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman and Geller families.

Author: William Lubinger Source: Case Western Reserve Contact: William Lubinger Case Western Reserve Image: The image is credited to Neuroscience News

Original Research: The findings will appear in Nature Neuroscience

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Neuroscience

Anxiety Drives Wishful Thinking to Risky Levels – Neuroscience News

Summary: Individuals tend to become overly optimistic in situations marked by insecurity and anxiety, potentially to their detriment. The research, involving more than 1,700 participants, demonstrated that people are less accurate in recognizing patterns linked to negative outcomes, like electrical shocks or monetary loss, indicating a clear bias towards wishful thinking. Interventions to reduce this bias included simplifying tasks to reduce uncertainty and offering rewards for accuracy, which showed mixed results. The findings suggest that while wishful thinking can help cope with stress, it may also hinder necessary actions in critical situations like health or environmental crises.

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Source: University of Amsterdam

Everyone indulges in wishful thinking now and again. But when is that most likely to happen and when could it actually be harmful?

A new study, led by the University of Amsterdam (UvA), demonstrates unequivocally that the greater the insecurity and anxiety of a situation, the more likely people are to become overly optimistic even to the point where it can prevent us from taking essential action.

The studys results have now been published in the journalAmerican Economic Review.

People arent purely truth-seekers many beliefs are influenced by emotions and driven by what is pleasant or comforting. Like belief in an afterlife or optimism about health outcomes, says Jol van der Weele, professor of Economic Psychology at the UvA. Working alongside professor of Neuroeconomics Jan Engelmann and an international team, Van der Weele set out to answer whether people become overly optimistic when facing potential hardships.

So far studies havent provided clear evidence for wishful thinking, with many not backing up the idea, explains Engelmann. But these mainly focused on positive outcomes, like winning a lottery. We examined how both positive and negative outcomes influence biased beliefs.

Choosing the most pleasant outcome

Understanding self-deception and its causes is difficult in real-world situations. The study involved a set of experiments with over 1,700 participants, conducted in a lab and online.

Participants were briefly shown various patterns, such as sets of differently oriented stripes or coloured dots, and were asked what kind of pattern they saw. Some of these patterns were linked to a negative outcome to induce anxiety, either a mild and non-dangerous electrical shock (in the lab) or a loss of money (online).

We wanted to see if people make more mistakes in recognising patterns associated with a negative outcome, thinking it was actually a harmless pattern. That would indicate wishful thinking, explains Van der Weele.

The study consistently found that participants were less likely to correctly identify patterns associated with a shock or loss.

The participants tended to see a pattern that aligned with what was more desirable, Engelmann says.

Previous research looked at wishful thinking related to positive outcomes and found mixed results, with many studies not finding an effect. Our study demonstrates very clearly thatthe negative emotionof anxiety about an outcome leads to wishful thinking.

Making people more realistic

The researchers also tested interventions designed to make people more realistic. The first involved making the patterns easier to recognise.

Reducing uncertainty did indeed turn out to reduce wishful thinking, says Van der Weele.

The second intervention was to offer higher potential earnings for correct pattern recognition. This intervention had little effect, except when participants could gather more evidence about the exact pattern they were shown.

When people had more time to collect evidence and were better rewarded for a correct answer, they became more realistic, explains Engelmann.

Finally, in the experiments where negative outcomes were replaced by positive outcomes, participants showed no wishful thinking. According to the authors this shows that reducing negative emotions can lessen overoptimism.

Wishful thinking in the real world

The authors recognise that wishful thinking can be useful because it helps us deal with bad feelings and manage uncertainty.

Engelmann: Wishful thinking is important for humans in coping with anxiety about possible future events.

For Van der Weele and Engelmann, the concern is situations in which too much optimism stops people from getting the information they need or from acting in a way that would benefit them.

People can get too hopeful when things are uncertain. We observe this happening with climate change, when financial markets fluctuate, and even in personal health situations when people avoid medical help because they think everything will be fine. We need to know more about when wishful thinking helps and when it hurts.

Author: Laura Erdtsieck Source: University of Amsterdam Contact: Laura Erdtsieck University of Amsterdam Image: The image is credited to Neuroscience News

Original Research: Open access. Anticipatory Anxiety and Wishful Thinking by Jol van der Weele et al. American Economic Review

Abstract

Anticipatory Anxiety and Wishful Thinking

Across five experiments (N = 1,714), we test whether people engage in wishful thinking to alleviate anxiety about adverse future outcomes.

Participants perform pattern recognition tasks in which some patterns may result in an electric shock or a monetary loss.

Diagnostic of wishful thinking, participants are less likely to correctly identify patterns that are associated with a shock or loss.

Wishful thinking is more pronounced under more ambiguous signals and only reduced by higher accuracy incentives when participants cognitive effort reduces ambiguity.

Wishful thinking disappears in the domain of monetary gains, indicating that negative emotions are important drivers of the phenomenon.

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Anxiety Drives Wishful Thinking to Risky Levels - Neuroscience News

Neuroscience

Prolonged Progestogen Use Linked to Brain Tumor Risk – Neuroscience News

Summary: A new study highlights a significant link between prolonged use of certain progestogen hormone drugs and an increased risk of developing intracranial meningioma, a type of brain tumor. Researchers analyzed data from 18,061 women who underwent surgery for intracranial meningioma, comparing their progestogen use to 90,305 controls.

The study found that prolonged use of specific progestogens, including medrogestone, medroxyprogesterone acetate, and promegestone, is associated with an elevated risk of requiring surgery for meningioma. This research underscores the urgent need for further studies to understand this risk fully, especially given the widespread use of these hormones in treating conditions like endometriosis and as part of contraceptive methods.

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Source: BMJ

Prolonged use of certain progestogen hormone drugs is associated with an increased risk of developing a type of brain tumour known as an intracranial meningioma, finds a study from France published byThe BMJtoday.

The researchers say this study is the first to assess the risk associated with progestogens used by millions of women worldwide, and further studies are urgently needed to gain a better understanding of this risk.

Progestogens are similar to the natural hormone progesterone, which are widely used for gynaecological conditions such as endometriosis and polycystic ovary syndrome, and in menopausal hormone therapy and contraceptives.

Meningiomas are mostly non-cancerous tumours in the layers of tissue (meninges) that cover the brain and spinal cord. Factors such as older age, female sex, and exposure to three high-dose progestogens (nomegestrol, chlormadinone, and cyproterone acetate) are already known to increase the risk of meningioma.

But there are many other progestogens for which the risk of meningioma associated with their use has not been estimated individually.

To address this knowledge gap, researchers set out to evaluate the real life risk of intracranial meningioma requiring surgery in women associated with use of several progestogens with different routes of administration.

They used data from the French national health data system (SNDS) for 18,061 women (average age 58) who underwent intracranial meningioma surgery from 2009-18.

Each case was matched to five control women without intracranial meningioma (total 90,305) by year of birth and area of residence.

The progestogens examined were progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and levonorgestrel intrauterine systems.

For each progestogen, use was defined as at least one prescription in the year before hospital admission or within 3-5 years for levonorgestrel intrauterine systems.

Use of at least one of the three high-dose progestogens known to increase the risk of meningioma in the 3 years before hospital admission was also recorded to minimise bias.

After taking account of other potentially influential factors, prolonged use (a year or more) of medrogestone was associated with a 4.1-fold increased risk of intracranial meningioma requiring surgery.

Prolonged use of medroxyprogesterone acetate injection was associated with a 5.6-fold increased risk, and prolonged use of promegestone was linked to a 2.7-fold increased risk.

There appeared to be no such risk for less than one year of use of these progestogens.

As expected, there was also an excess risk of meningioma for women exposed to chlormadinone acetate, nomegestrol acetate, and cyproterone acetate, all of which are known to increase the risk of meningioma.

However, results showed no excess risk of meningioma for progesterone, dydrogesterone, or the widely used hormonal intrauterine systems, regardless of the dose of levonorgestrel they contained.

No conclusions could be drawn about dienogest or hydroxyprogesterone as the number of exposed individuals was too small.

This is an observational study so cant establish cause and effect, and the authors acknowledge that the SNDS database lacked information on all the clinical details and medical indications for which progestogens are prescribed. Nor were they able to account for genetic predisposition and exposure to high dose radiation.

However, they say, given that medroxyprogesterone acetate is estimated to be used for birth control by 74 million women worldwide, the number of attributable meningiomas may be potentially high.

Further studies using other sources of data are urgently needed to gain a better understanding of this risk, they conclude.

Author: BMJ Media Relations Source: BMJ Contact: BMJ Media Relations BMJ Image: The image is credited to Neuroscience News

Original Research: The findings will appear in The BMJ

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Prolonged Progestogen Use Linked to Brain Tumor Risk - Neuroscience News