Category: Neurology

Categories : Injury & Trauma NeurologyTags :

Concussions in Amateur Sport not Linked to Long-term Cognitive Effects

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Photo by Olga Guryanova on Unsplash

The impact of concussion while playing sport is different in those who don’t play professionally, says new research.

Sports-related concussions (SRC) may not be associated with long-term cognitive risks for non-professional athletes, a study led by a UNSW medical researcher suggests. In fact, study participants who had experienced an SRC had better cognitive performance in some areas than those who had never suffered a concussion, pointing to potential protective effects of sports participation.

Published in the Journal of Neurology, Neurosurgery and Psychiatry, the research reveals that individuals who reported experiencing any SRC during their lifetime had a marginally better cognitive performance than those who reported no concussions.

The study, a collaboration between researchers at UNSW Sydney, the University of Oxford, the University of Exeter and Harvard University, analysed data from more than 15 000 participants from the UK-based PROTECT study of 50- to 90-year-olds. This ongoing research aims to understand brain ageing and cognitive decline.

“Our findings suggest that there is something about playing sport, even though a person may experience concussion, that may be beneficial for long-term cognitive outcomes,” says lead author Dr Matt Lennon MD, PhD, at UNSW Medicine & Health.

“While it may be that those who play sports have had access to better education and more resources, we controlled for these factors in the analysis, so that doesn’t explain the result. We hypothesise that there may be physical, social and long-term behavioural effects of sport that may make for healthier adults in late-life,” said Dr Lennon.

Largest study of long-term effects of sports concussions

The study is the largest to date examining the long-term cognitive effects of SRC. Researchers collected lifetime concussion histories from 15 214 participants using the Brain Injury Screening Questionnaire. Among them, 6227 (39.5%) reported at least one concussion and 510 (3.2%) at least one moderate-severe concussion. On average, participants reported suffering their last head injury an average of 29 years prior to the study and their first head injury an average of 39 years earlier.

Researchers then compared cognitive function among individuals with 0, 1, 2 and 3+ SRCs and 0, 1, 2 and 3+ non-sports-related concussions (nSRCs)  (i.e. from falls, car accidents, assaults and other causes). The SRC group showed 4.5 percentile rank better working memory than those who hadn’t experienced an SRC, and 7.9% better reasoning capacity than those without concussions.

Those with one SRC also had better verbal reasoning and attention compared to those with no SRC.

Conversely, participants with 3+ nSRCs – so things like accident and assaults – had worse processing speed and attention, and a declining trajectory of verbal reasoning with age.

“This study suggests that there could be long term benefits from sport which could outweigh any negative effects of concussions, which could have important implications for policy decisions around contact sport participation. It may also be that non-sports related head injuries lead to greater brain damage than sports-related concussions,” said senior author Professor Vanessa Raymont from the University of Oxford and Oxford Health NHS Foundation Trust.

The researchers say the study had some limitations.

“The retrospective design of the study, with elderly participants often recalling details of events over three decades in the past, may have affected the reporting of head injuries, even though we used a well-validated head injury screening tool,” said Prof. Raymont.

Study implications

The study looked at mid-to-late-life people who experienced SRC years earlier, whereas most other studies on SRC focus on younger athletes in the immediate period after their head injuries, where cognitive effects are most salient.

“While these results do not indicate the safety of any sport in particular, they do indicate that overall sports may have greater beneficial effects for long-term cognitive health than the damage it causes, even in those who have experienced concussion,” said Dr Lennon.

“This finding should not be overstated – the beneficial effects were small and in people who had two or more sports-related concussions there was no longer any benefit to concussion. Additionally, this study does not apply to concussions in professional athletes whose head injuries tend to be more frequent, debilitating and severe.”

Anne Corbett, Professor at Exeter University and the lead investigator of the PROTECT study, said: “What we see emerging is a completely different profile of brain health outcomes for people who have concussions as a result of sport compared to those that are not related to sport. Concussions that occur during sport do not lead to brain health concerns whereas other concussion types do, especially when people experience multiple concussions. In fact, people who take part in sport seem to have better brain health regardless of whether they have had a concussion whilst taking part or not.”

Source: University of New South Wales

Categories : Cancer NeurologyTags :

Scars of Destroyed Brain Tumours are Fertile Grounds for Recurrence

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Types of tumour cells. Credit: Scientific Animations CC4.0

A Ludwig Cancer Research study has discovered that recurrent tumours of the aggressive brain cancer glioblastoma multiforme (GBM) grow out of the fibrous scars of malignant predecessors destroyed by interventions such as radiotherapy, surgery and immunotherapy.

Led by Ludwig Lausanne’s Johanna Joyce, Spencer Watson and alumnus Anoek Zomer and published in the current issue of Cancer Cell, the study describes how these scars enable the regrowth of tumours and identifies drug targets to sabotage their malignant support. It also demonstrates the efficacy of such combination therapies in preclinical trials using mouse models of GBM.

“We’ve identified fibrotic scarring as a key source of GBM resurgence following therapy, showing how it creates a protective niche for the regrowth of the tumor,” said Joyce. “Our findings suggest that blocking the process of scarring in the brain by adding anti-fibrosis agents to current treatment strategies could help prevent glioblastoma from recurring and improve the outcomes of therapy.”

There is a great need for such interventions. GBM is the most common and aggressive form of brain cancer in adults. Despite considerable effort to develop effective therapies for the cancer, the average life expectancy of patients remains around 14 months following diagnosis.

The origins of the current study date back to 2016, when the Joyce lab reported in the journal Science its examination in mouse models of strategies to overcome resistance to a promising immunotherapy for the treatment of GBM. That experimental therapy, which inhibits signalling by the colony stimulating factor-1 receptor (CSF-1R) and currently in clinical trials, targets immune cells known as macrophages and their brain-resident versions, microglia, both of which are manipulated by GBM cells to support tumour growth and survival.

The Joyce lab has demonstrated that CSF-1R inhibition reprograms these immune cells into an anti-tumour state and so induces significant tumour regression. Yet, as the Science study showed, about half the mice show relapse following an initial response to the therapy. “What was most remarkable about that observation was that every single time a brain tumour recurred following immunotherapy, it regrew right next to a scar that had formed at the original site of a tumour,” said Joyce.

In the current study, Joyce, Watson, Zomer and their colleagues examined tumour samples obtained from patients undergoing GBM therapy and showed that fibrotic scarring occurs following therapy in humans as well – and that it is similarly associated with tumour recurrence. They also showed that the fibrotic scarring occurs in response to not only immunotherapy but also following the surgical and radiological removal of tumours.

To explore how fibrosis contributes to relapse, the researchers applied an integrated suite of advanced technologies to analyze the cellular and molecular geography of the scars and the microenvironment of resurgent tumors.

These technologies include the analysis of global gene expression in individual cells, the comprehensive analysis of proteins in the tissues as well a workflow and AI-powered suite of analytical methods for the spatial analysis of tissues named hyperplexed immunofluorescence imaging (HIFI). Recently developed by Watson and colleagues in the Joyce lab, HIFI permits the simultaneous visualisation of multiple molecular markers in and around cells across broad cross-sections of tissues, enabling the generation of granular maps of the tumour microenvironment.

“Applied together, these advanced methods allowed us to see exactly how fibrotic scars form,” said Watson. “They revealed that the fibrosis serves as a kind of protective cocoon for residual cancer cells and pushes them into a dormant state in which they are largely resistant to therapy. We found that it also shields them from surveillance and elimination by the immune system.”

Integrated analyses of the tissue microenvironment following therapy revealed that the descendants of cells associated with tumor-feeding blood vessels become functionally altered to resemble fibroblasts—fiber-producing cells commonly involved in wound-healing. These perivascular-derived fibroblast-like (PDFL) cells fan out across the region previously occupied by the regressing tumor, where they mediate the generation of fibrotic scars. These cells, the researchers found, are especially activated by neuroinflammation and immune factors known as cytokines, most notably one called transforming growth factor-β (TGF-β).

“To see if targeting fibrotic scarring could improve therapeutic outcomes for GBM, we devised a treatment regimen using existing drugs to block TGF-β signaling and suppress neuroinflammation in combination with CSF-1R inhibition and evaluated it in preclinical trials using mouse models of GBM,” said Joyce. “We also timed these additional treatments to coincide with the period of maximal PDFL activation identified by our studies. Our results show that the drug combination inhibited fibrotic scarring, diminished the numbers of surviving tumor cells and extended the survival of treated mice compared to controls.”

The researchers suggest that approaches to limit fibrotic scarring could significantly improve outcomes for GBM patients receiving surgical, radiation or macrophage-targeting therapies. Additional research, they note, will likely yield even better drug targets for such combination therapies.

Source: Ludwig Institute for Cancer Research

Categories : Injury & Trauma NeurologyTags :

Engineered T Cells aid the Recovery of Spinal Cord Injury

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View of the spinal cord. Credit: Scientific Animations CC4.0

In a recent study published in Nature, researchers prevented T cells from causing the normal autoimmune damage that comes with spinal cord injury, sparing neurons and successfully aiding recovery in mouse models.

In spinal cord injury, the wound site attracts a whole host of peripheral immune cells, including T cells, which result in both beneficial and deleterious effects. Notably, antigen-presenting cells activate CD4+ T cells to release cytokines, ultimately leading to neuroinflammation and tissue destruction. This neuroinflammation is notably most pronounced during the acute phase of spinal cord injury. The problem is that these same T cells have a neuroprotective effect initially, only later developing autoimmunity and attacking the injury site.

Using single cell RNA sequencing, the researchers found that CD4+ T cell clones in mice showed antigen specificity towards self-peptides of myelin and neuronal proteins. Self-peptides have been implicated in a wide range of autoimmune conditions.

Using mRNA techniques, the researchers edited the T cell receptor, so that they shut off after a few days. In mouse models of spinal cord injury, they showed notable neuroprotective efficacy, partly as a result of modulating myeloid cells via interferon-γ.

Their findings provided insights into the mechanisms behind the neuroprotective function of injury-responsive T cells. This will help pave the way for the future development of T cell therapies for central nervous system injuries, and perhaps treatments for neurodegenerative diseases such as Alzheimer’s.

Categories : Cancer NeurologyTags :

Glioma Cells can Also Fire off Electrical Signals in the Brain

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Source: Pixabay

Researchers at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital have uncovered a new cell type in human brain cancers. Their study, published in Cancer Cell, reveals that a third of the cells in glioma, fire electrical impulses. Interestingly, the impulses, also called action potentials, originate from tumour cells that are part neuron and part glia, supporting the groundbreaking idea that neurons are not the only cells that can generate electric signals in the brain.

The scientists also discovered that cells with hybrid neuron-glia characteristics are present in the non-tumour human brain. The findings highlight the importance of further studying the role of these newly identified cells in both glioma and normal brain function.

“Previous studies have shown that patient survival outcomes are associated with tumour proliferation and invasiveness, which are influenced by tumour intrinsic and extrinsic factors, including communication between tumour cells and neurons that reside in the brain,” said Dr Benjamin Deneen, professor in the Department of Neurosurgery at Baylor.

Researchers have previously described that glioma and surrounding healthy neurons connect with each other and that neurons communicate with tumours in ways that drive tumour growth and invasiveness. 

“We have known for some time now that tumour cells and neurons interact directly,” said first author Dr Rachel N. Curry, postdoctoral fellow in paediatrics – neuro oncology at Baylor, who was responsible for conceptualising the project. “But one question that always lingered in my mind was, ‘Are cancer cells electrically active?’ To answer this question correctly, we required human samples directly from the operating room. This ensured the biology of the cells as they would exist in the brain was preserved as much as possible.”

To study the ability of glioma cells to spike electrical signals and identify the cells that produce the signals, the team used Patch-sequencing, a combination of techniques that integrates whole-cell electrophysiological recordings to measure spiking signals with single-cell RNA-sequencing and analysis of the cellular structure to identify the type of cells.

The electrophysiology experiments were conducted by research associate and co-first author Dr Qianqian Ma in the lab of co-corresponding author associate professor of neuroscience Dr Xiaolong Jiang. This innovative approach has not been used before to study human brain tumour cells. “We were truly surprised to find these tumour cells had a unique combination of morphological and electrophysiological properties,” Ma said. “We had never seen anything like this in the mammalian brain before.”

“We conducted all these analyses on single cells. We analysed their individual electrophysiological activity. We extracted each cell’s content and sequenced the RNA to identify the genes that were active in the cell, which tells us what type of cell it is,” Deneen said. “We also stained each cell with dyes that would visualise its structural features.”

Integrating this vast amount of individual data required the researchers to develop a novel way to analyse it.

“To define the spiking cells and determine their identity, we developed a computational tool – Single Cell Rule Association Mining (SCRAM) – to annotate each cell individually,” said co-corresponding author, Dr Akdes Serin Harmanci, assistant professor of neurosurgery at Baylor.

“Finding that so many glioma cells are electrically active was a surprise because it goes against a strongly held concept in neuroscience that states that, of all the different types of cells in the brain, neurons are the only ones that fire electric impulses,” Curry said. “Others have proposed that some glia cells known as oligodendrocyte precursor cells (OPCs) may fire electrical impulses in the rodent brain, but confirming this in humans had proven a difficult task. Our findings show that human cells other than neurons can fire electrical impulses. Since there is an estimated 100 million of these OPCs in the adult brain, the electrical contributions of these cells should be further studied.”

“Moreover, the comprehensive data analyses revealed that the spiking hybrid cells in glioma tumours had properties of both neurons and OPC cells,” Harmanci said. “Interestingly, we found non-tumour cells that are neuron-glia hybrids, suggesting that this hybrid population not only plays a role in glioma growth but also contributes to healthy brain function.”

“The findings also suggest that the proportion of spiking hybrid cells in glioma may have a prognostic value,” said co-corresponding author Dr Ganesh Rao, professor and chair of neurosurgery at Baylor. “The data shows that the more of these spiking hybrid glioma cells a patient has, the better the survival outcome. This information is of great value to patients and their doctors.”

“This work is the result of extensive equal collaboration across multiple disciplines – neurosurgery, bioinformatics, neuroscience and cancer modelling – disciplines strongly supported by state-of-the-art groups at Baylor,” Deneen said. “The results offer an enhanced understanding of glioma tumours and normal brain function, a sophisticated bioinformatics pipeline to analyse complex cellular populations and potential prognostic implications for patients with this devastating disease.”

Source: Baylor College of Medicine

Categories : Injury & Trauma NeurologyTags :

More than Mobility: Gaining Independence after a Spinal Cord Injury

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International Spinal Cord Injury Day marked on 5 September 2024

Photo by Elevate on Unsplash

5 September 2024, International Spinal Cord Injury Day is commemorated on Thursday 5 September, drawing attention to the many ways people can be affected by spinal cord injury, creating awareness of prevention, and highlighting the possibilities for a fulfilling life after injury.

According to the World Health Organization, globally, over 15 million people are living with spinal cord injuries. Most of these cases are due to trauma, including falls, road traffic injuries or violence.

Jessica Morris, an occupational therapist at the Netcare Rehabilitation Hospital in Auckland Park, says one of the most critical aspects of care for those who’ve been impacted by spinal cord injuries is the importance of successful rehabilitation through a holistic, integrated approach from a multidisciplinary team.

“Many people just think it’s just about mobility. It’s so much more than that. Rehabilitation is complex because many different areas of our patients’ lives are affected.” Morris says they are fortunate that their team has so many different practitioners who can contribute to treating spinal cord injury patients, helping them regain a level of independence, which is vital to their self-confidence and sense of empowerment.

Dr Anrie Carstens,  a general practitioner with a particular interest in physical medicine and rehabilitation who practises at the Netcare Rehabilitation Hospital, says the message of Spinal Cord Injury Awareness Day has relevance all year round, as people with spinal cord injuries need to be incorporated into society.

“It’s an opportunity to tell people not to be nervous to talk to someone in a wheelchair. They’re just like you or me, and they just have special ways of moving around and managing their pain and different aspects of their bodies. With the help of proper rehabilitation, the person can be better integrated as a functional, contributing member of society.”

Dr Carstens says people should also be aware that if they or their loved ones are ever impacted by a spinal cord injury, professional support is available. “Don’t just go straight home after your hospital stay and try to do everything on your own. Instead, come to a specialised spinal cord injury unit like ours, with therapists, doctors and nursing staff who are well versed in spinal cord injury and know the finer nuances necessary to optimally treat the person and show them how best to cope with their injury.

“In the multidisciplinary approach, every practitioner has a role in getting the person back into the real world, whether it means going back home, back to school, back to work or wherever they were before their injury occurred.”

From doctors and nurses with specialised skills to physiotherapists, occupational therapists, social workers and psychologists, speech therapists, a prosthetist and dieticians, the team provides a broad person focussed rehabilitation service to both adults and children. Their aim is to optimise their patients’ independence level using specialised equipment and teaching specific techniques to help overcome the obstacles a person may face.

Dr Carstens says it’s rewarding work for the staff at the hospital, who build up enduring relationships with those they care for. “One of the highlights is to compare and see what the patient was like when you admitted them and then see on discharge how much they’ve grown, how they’ve gained confidence and become more independent. What’s even better is to see them after they’ve been discharged and observe how well they’ve coped and how they’ve integrated and adjusted to their environment. We build a relationship with our patients because they stay with us for quite a while, and we usually have checkups every year after the person is discharged, often for life. We get to see them grow and thrive outside the healthcare setting, and we need more awareness about how much it is possible for people with spinal cord injuries to achieve.” 

Categories : NeurologyTags :

White Matter may Aid Recovery from Spinal Cord Injuries

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View of the spinal cord. Credit: Scientific Animations CC4.0

Injuries, infection and inflammatory diseases that damage the spinal cord can lead to intractable pain and disability but some degree of recovery may be possible. The question is, how best to stimulate the regrowth and healing of damaged nerves.

At the Vanderbilt University Institute of Imaging Science (VUIIS), scientists are focusing on a previously understudied part of the brain and spinal cord – white matter, which is made up of axons that relay signals. Their discoveries could lead to treatments that restore nerve activity through the targeted delivery of electromagnetic stimuli or drugs.

In a recent paper published in the Proceedings of the National Academy of Sciences, Anirban Sengupta, PhD, John Gore, PhD, and their colleagues report the detection of signals from white matter in the spinal cord in response to a stimulus that are as robust as grey matter signals.

“In the spinal cord, the white matter signal is quite large and detectable, unlike in the brain, where it has less amplitude than the grey matter (signal),” said Sengupta, research instructor in Radiology and Radiological Sciences at Vanderbilt University Medical Center.

“This may be due to the larger volume of white matter in the spinal cord compared to the brain,” he added. Alternatively, the signal could represent “an intrinsic demand” in metabolism within the white matter, reflecting its critical role in supporting grey matter.

For several years, Gore, who directs the VUIIS, and his colleagues have used functional magnetic resonance imaging (fMRI) to detect blood oxygenation-level dependent (BOLD) signals, a key marker of nervous system activity, in white matter.

Last year, they reported that when participants undergoing fMRI perform a task, like wiggling their fingers, BOLD signals increase in white matter throughout the brain.

The current study monitored changes in BOLD signals in the white matter of the spinal cord at rest and in response to a vibrotactile stimulus applied to the fingers in an animal model. In response to stimulation, white matter activity was higher in “tracts” of ascending fibres that carry the signal from the spine to the brain.

This result is consistent with white matter’s known neurobiological function, the researchers noted. White matter contains non-neuronal glial cells that do not produce electrical impulses, but which regulate blood flow and neurotransmitters, the signaling molecules that transmit signals between nerve cells.

Much remains to be learned about the function of white matter in the spinal cord. But the findings from this research may help in improved understanding of diseases that affect white matter in the spinal cord, including multiple sclerosis, Sengupta said.

“We will be able to see how activity in the white matter changes in different stages of the disease,” he said. Researchers also may be able to monitor the effectiveness of therapeutic interventions, including neuromodulation, in promoting recovery following spinal cord injury.

Source: Vanderbilt University Medical Center

Categories : General Interest NeurologyTags :

fMRI Discovers Where Love Resides in the Brain

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The image represents a statistical average of how different types of love light up different regions of the brain. Photo: Pärttyli Rinne et al 2024, Aalto University.

We use the word ‘love’ in a bewildering range of contexts, from sexual adoration to parental love or the love of nature. Now, more comprehensive imaging of the brain may shed light on why we use the same word for such a diverse collection of human experiences.

“You see your newborn child for the first time. The baby is soft, healthy and hearty – your life’s greatest wonder. You feel love for the little one.”

The above statement was one of many simple scenarios presented to 55 parents, self-described as being in a loving relationship. Researchers from Aalto University utilised functional magnetic resonance imaging (fMRI) to measure brain activity while subjects mulled brief stories related to six different types of love.

“We now provide a more comprehensive picture of the brain activity associated with different types of love than previous research,” says Pärttyli Rinne, the philosopher and researcher who coordinated the study. “The activation pattern of love is generated in social situations in the basal ganglia, the midline of the forehead, the precuneus and the temporoparietal junction at the sides of the back of the head.”

Love for one’s children generated the most intense brain activity, closely followed by romantic love.

“In parental love, there was activation deep in the brain’s reward system in the striatum area while imagining love, and this was not seen for any other kind of love,” says Rinne. Love for romantic partners, friends, strangers, pets and nature were also part of the study, which was published in the journal Cerebral Cortex.

According to the research, brain activity is influenced not only by the closeness of the object of love, but also by whether it is a human being, another species or nature.

Unsurprisingly, compassionate love for strangers was less rewarding and caused less brain activation than love in close relationships. Meanwhile, love of nature activated the reward system and visual areas of the brain, but not the social brain areas.

Pet-owners identifiable by brain activity

The biggest surprise for the researchers was that the brain areas associated with love between people ended up being very similar, with differences lying primarily in the intensity of activation. All types of interpersonal love activated areas of the brain associated with social cognition, in contrast to love for pets or nature – with one exception.

Subjects’ brain responses to a statement like the following, on average, revealed whether or not they shared their life with a furry friend:

“You are home lolling on the couch and your pet cat pads over to you. The cat curls up next to you and purrs sleepily. You love your pet.”

“When looking at love for pets and the brain activity associated with it, brain areas associated with sociality statistically reveal whether or not the person is a pet owner. When it comes to the pet owners, these areas are more activated than with non-pet owners,” says Rinne.

Love activations were controlled for in the study with neutral stories in which very little happened. For example, looking out the bus window or absent-mindedly brushing your teeth. After hearing a professional actor’s rendition of each ‘love story’, participants were asked to imagine each emotion for 10 seconds.

This is not the first effort at finding love for Rinne and his team, which includes researchers Juha Lahnakoski, Heini Saarimäki, Mikke Tavast, Mikko Sams and Linda Henriksson. They have undertaken several studies seeking to deepen our scientific knowledge of human emotions. The group released research mapping subjects’ bodily experiences of love a year ago, with the earlier study also linking the strongest physical experiences of love with close interpersonal relationships.

Not only can understanding the neural mechanisms of love help guide philosophical discussions about the nature of love, consciousness, and human connection, but also, the researchers hope that their work will enhance mental health interventions in conditions like attachment disorders, depression or relationship issues.

Source: Aalto University

Categories : Ageing NeurologyTags :

Brain Ages at Different Paces According to Social and Physical Environments

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An international study employing advanced measurements of brain ageing on a wide range of participants found that people from more disadvantaged countries and backgrounds had older biological ages for their brains compared to chronological ages. The results are published in Nature Medicine.

The pace at which the brain ages can vary significantly among individuals.  This difference between biological and chronological ages may be affected by environmental factors like pollution and social factors like income or health inequalities, especially in older people and those with dementia. Until now, it was unclear how these combined factors could either accelerate or delay brain ageing across diverse geographical populations. 

The study used advanced brain clocks based on deep learning of brain networks, involved a diverse dataset of 5306 participants from 15 countries. By analysing data from functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), the researchers quantified brain age gaps in healthy individuals and those with neurodegenerative conditions such as mild cognitive impairment (MCI), Alzheimer’s disease, and frontotemporal lobe degeneration (FTLD). 

Participants with a diagnosis of dementia, particularly Alzheimer’s disease, exhibited the most critical brain age gaps. The research also highlighted sex differences in brain ageing, with women in Latin American and Caribbean countries showing greater brain age gaps, particularly in those with Alzheimer’s disease. These differences were linked to biological sex and gender disparities in health and social conditions. Variations in signal quality, demographics, or acquisition methods did not explain the results. These findings underscore the role of environmental and social factors in brain health disparities. 

The findings of this study have profound implications for neuroscience and brain health, particularly in understanding the interaction between macro factors (exposome) and the mechanisms that underlie brain ageing across diverse populations in healthy ageing and dementia. The study’s approach, which integrates multiple dimensions of diversity into brain health research, offers a new framework for personalised medicine. This framework could be crucial for identifying individuals at risk of neurodegenerative diseases and developing targeted interventions to mitigate these risks. Moreover, the study’s results highlight the importance of considering the biological embedding of environmental and social factors in public health policies. Policymakers can reduce brain age gaps and promote healthier ageing across populations by addressing issues such as socioeconomic inequality and environmental pollution. 

Source: University of Surrey

Categories : NeurologyTags :

Pulling Back the Curtain on the Brain Circuit for Memory Recall

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Photo by Anna Shvets

Deep within either hemisphere of the brain is the “claustrum complex”, which contributes to consciousness and awareness. Many diseases known to be related to higher cognitive function, such as Alzheimer’s, schizophrenia, and ADD/ADHD, are also closely linked to abnormal function of this particular part of the brain. But how the different parts of the claustrum complex work or how its circuits and communication system are organised is not fully understood.

Researchers at Aarhus University have now uncovered this, and their results identify, down to the cellular level, which part of the claustrum complex controls our ability to discriminate familiar and novel things.

“Our study focuses on an area of the claustrum called the ‘endopiriform,’ which is a relatively unknown brain structure despite its unique brain network and cellular properties,” explains Asami Tanimura, an associate professor and the lead researcher of the study appearing as a preprint in eLife.

“For the first time, we have dissected the circuit of endopiriform to the hippocampus, and demonstrated how this pathway is crucial for recognition memory.”

In mouse models, researchers were able to observe how the mice’s behaviour changed when they respectively ‘turned on’ and ‘turned off’ the activity in this specific cell group.

Asami explains: “We observed that the cells in the endopiriform were active when the mice interacted with new conspecifics or objects, and when we inhibited this cell group, it reduced the mice’s ability to distinguish novel mouse or object from familiar ones.”

Based on this, the researchers concluded that this specific cell group in the claustrum seems to play a key role in sending memory-guided attention signal to the hippocampus.

“This is entirely new knowledge about this small but important part of the brain, and it gives us a unique understanding of the special circuit involved in recognition memory,” explains Asami.

What this knowledge might mean, and whether it could lead to the development of new treatment methods targeted at disorders in this part of the brain, remains to be seen. However, Asami and her colleagues are optimistic:

“To develop effective treatment methods, a very detailed understanding of the cells’ circuits is required. With our study, we have at least opened a door that has previously been closed in terms of specific role of the endopiriform-hippocampal circuit on higher cognitive function.”

Source: Aarhus University

Categories : Cancer NeurologyTags :

Serotonin-producing Neurons Regulate Malignancy in Ependymoma Brain Tumours

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Credit: National Cancer Institute

A study published in Nature reveals the functional relevance of tumour-neuron interactions that regulate the growth of ependymoma brain tumours, one of the most common types in children. The study, conducted by researchers at Baylor College of Medicine and St. Jude Children’s Research Hospital, highlights how neuronal signalling, modifications in DNA-associated proteins and developmental programs are intertwined to drive malignancy in brain cancer.

“Ependymomas are the third most common type of paediatric brain tumours,” said co-corresponding author, Dr Benjamin Deneen professor in the Department of Neurosurgery. “These tumours are aggressive, resistant to chemotherapy and lack tumour-specific therapies, leading to poor survival.”

“We have not made an impact on patient survival in the last three decades. A major factor has been a poor understanding of the disease. The motivation of our collaborative work with the Deneen lab is to dissect the biology of these tumours as a basis for developing new therapies,” said co-corresponding author Dr Stephen Mack, associate member at St. Jude Children’s Research Hospital and member of the Department of Neurobiology, Neurobiology and Brain Tumor Program and Center of Excellence in Neuro-Oncology Sciences.

Previous studies have shown in other types of brain tumours that brain activity surrounding the tumour can influence its growth. “In the current study, we investigated whether brain activity played a role in ependymoma growth, specifically in a very aggressive type driven by a protein called ZFTA-RELA,” said first author Hsiao-Chi Chen, a graduate student in the Deneen lab. “In collaboration with the Mack lab, we developed an animal model to study this rare paediatric brain tumour and validated these findings in human tumour samples.”

The researchers discovered evidence of abnormal neuronal activity in ependymoma’s environment and investigated whether it affected ependymoma growth. They found that while hyperactivity of some neural circuits promoted tumour growth, hyperactivity of other neural circuits surprisingly reduced tumour growth, which had not been described before. Their study revealed a novel chain of events at play that regulates tumour growth, which may hold therapeutic applications.

“First, we found that normal neurons located in the brain region called dorsa raphe nucleus (dRN) project towards the cortex, where ependymoma grows. These neurons secrete serotonin, a brain chemical that carries messages between nerve cells, which surprisingly slows tumour growth,” Chen said.

Interestingly, ependymoma cells carry a serotonin transporter, a molecule that imports serotonin within the cell. “We were surprised to discover that serotonin enters ependymoma cells and binds to histone H3, a protein that is tightly associated with DNA,” Chen said. “Histone serotonylation, the addition of serotonin to histone, regulated tumour growth. Promoting it enhanced tumour growth while preventing it slowed down ependymoma growth in animal models.”

“Discovering histone serotonylation in ependymoma piqued our interest because a previous study from our lab had revealed that adding serotonin to histones affects which genes the cell turns on,” Deneen said.

The team discovered that histone serotonylation in ependymoma increases the expression of transcription factors, genes that regulate the expression of other genes,” Chen said. “We focused on transcription factor ETV5 whose overexpression accelerated tumour growth. But how does it do it?”

The next experiments showed that ETV5 expression triggers changes in the 3D structure of chromatin, the combination of DNA and proteins that forms chromosomes. The 3D changes prevent the activation of genes encoding neurotransmitters, molecules that mediate neural activity. The team focused on a neurotransmitter called neuropeptide Y (NPY) and found that growing tumours have little NPY. Restoring the levels of NPY in tumours slowed down tumour progression and tumour-associated neural hyperactivity through the remodeling of surrounding synapses or neuron-to-neuron communication.

“We knew that brain tumours release factors that remodel synapses towards hyperactivity. Here we found the opposite also can happen, that ependymoma tumours can release factors that suppress excitatory synaptic remodeling and that repressing this mechanism is essential for tumour progression,” Deneen said.

“I am excited that this work has redefined our understanding of how brain tumour cells grow, and how they take advantage of factors in their surrounding environment to initiate tumours,” Mack said. “I am equally excited that this work has revealed many new avenues for research that may in the future lead to new therapies, which is desperately needed for this devastating disease.”

Source: Baylor College of Medicine