Tag: 4/6/25

Categories : Neurodegenerative DiseasesTags : Leave a comment

New Immune Solution Suggests Taking the STING out of Alzheimer’s

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A new way of thinking about Alzheimer’s disease has yielded a discovery that could be the key to stopping the cognitive decline seen in Alzheimer’s and other neurodegenerative diseases.

University of Virginia School of Medicine scientists have been investigating the possibility that Alzheimer’s is caused, at least in part, by the immune system’s wayward attempts to fix DNA damage in the brain. Their research reveals that an immune molecule called STING drives the formation of the harmful plaques and protein tangles thought responsible for Alzheimer’s. Blocking the molecule protected lab mice from mental decline, the researchers say.

An important player in the brain’s immune system, STING also may be a key contributor to Parkinson’s disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), dementia and other memory-robbing conditions. That means that developing treatments to control its activity could have far-reaching benefits for many patients facing now-devastating diagnoses.

“Our findings demonstrate that the DNA damage that naturally accumulates during aging triggers STING-mediated brain inflammation and neuronal damage in Alzheimer’s disease,” said researcher John Lukens, PhD, director of UVA’s Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases. “These results help to explain why aging is associated with increased Alzheimer’s risk and uncover a novel pathway to target in the treatment of neurodegenerative diseases.”

Alarming Trends in Alzheimer’s

Alzheimer’s is a growing problem, with researchers working frantically to find ways to better understand and treat the condition.

The causes of Alzheimer’s remain murky, but scientists are increasingly coming to appreciate the role of the immune system in the disease’s development. STING is part of that immune response; the molecule helps direct the clearance of viruses and stressed cells harboring DNA damage.

While STING is an important defender of the brain, it can also become hyperactive and cause harmful inflammation and tissue damage. That had Lukens and his team eager to determine what part it could be playing in Alzheimer’s. Blocking the molecule’s activity in lab mice, they found, helped prevent Alzheimer’s plaque formation, altered the activity of immune cells called microglia and redirected the workings of important genes, among other effects.

“We found that removing STING dampened microglial activation around amyloid plaques, protected nearby neurons from damage and improved memory function in Alzheimer’s model mice,” said researcher Jessica Thanos, part of UVA’s Department of Neuroscience and Center for Brain Immunology and Glia (BIG Center). “Together, these findings suggest that STING drives detrimental immune responses in the brain that exacerbate neuronal damage and contribute to cognitive decline in Alzheimer’s disease.”

Promising Treatment Target

While scientists have been investigating other molecules thought to be important in Alzheimer’s, STING makes for a particularly attractive target for developing new treatments, the UVA Health researchers say. That’s because blocking STING appears to slow both the buildup of amyloid plaques and the development of tau tangles, the two leading candidates for the cause of Alzheimer’s. Other molecules lack that robust involvement, and, further, could be targeted only at very specific – and very limited – stages in the disease’s progression.

“We are only beginning to understand the complex role of innate immune activation in the brain, and this is especially true in both normal and pathological aging,” Thanos said. “If we can pinpoint which cells and signals sustain that activation, we will be in a much better position to intervene effectively in disease.”

While Lukens’ pioneering research has opened new doors in the fight against Alzheimer’s, much more work will need to be done to translate the findings into treatments. For example, scientists will need to better understand STING’s roles in the body – such as in the immune system’s response to cancer – to ensure any new treatment doesn’t cause unwanted side effects.

But those are the types of big questions that Lukens and his collaborators at the Harrison Family Translational Research Center are eager to tackle as part of their efforts to fast-track new treatments and, eventually, they hope, cures.

“Our hope is that this work moves us close to finding safer and more effective ways to protect the aging brain, as there is an urgent need for treatments that can slow or prevent neuronal damage in Alzheimer’s,” Lukens said. “Shedding light on how STING contributes to that damage may help us target similar molecules and ultimately develop effective disease-modifying treatments.”

Source: University of Virginia Health System

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Brain Training Game Offers New Hope for Drug-free Pain Management

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An animated jellyfish floats through water in the PainWaive game. Image: PainWaive

The first trial of an interactive game that trains people to alter their brain waves has shown promise as a treatment for nerve pain – offering hope for a new generation of drug-free treatments.

You’re staring at a jellyfish drifting through inky black water on a screen. As your mind calms, the water turns turquoise. Nothing else seems to change, but the headset you’re wearing has picked up a subtle shift in your brainwaves and the game responds by altering the imagery. Now, for the first time, you can see your brain activity change. And by seeing it, you can practice making it happen again.

The game is part of PainWaive, a drug-free treatment for nerve pain developed by UNSW. Combining a game-like app and a brain-monitoring headset, PainWaive teaches users how to regulate the abnormal brain activity linked to chronic nerve pain, offering a potential in-home, non-invasive alternative to opioids.

The first trial of the treatment, led by Professor Sylvia Gustin and Dr Negin Hesam-Shariati from UNSW’s NeuroRecovery Research Hub, has delivered promising results, published in the Journal of Pain.

The study compared hundreds of measures across participants’ pain and related issues like pain interference before, during and after four weeks of interactive game play. Their brain activity was tracked via EEG (electroencephalogram) headsets, with the app responding in real time to shifts in brainwave patterns.

Three out of the four participants showed significant reductions in pain, particularly nearing the end of the treatment. Overall, the pain relief achieved by the three was comparable to or greater than that offered by opioids.

“Restrictions in the study’s size, design and duration limit our ability to generalise the findings or rule out placebo effects,” Dr Hesam-Shariati says. 

“But the results we’ve seen are exciting and give us confidence to move to the next stage and our larger trial.”

The PainWaive project builds on UNSW Professor Sylvia Gustin’s seminal research into changes in the brain’s thalamus – a central relay hub in the brain – associated with nerve (neuropathic) pain.

“The brainwaves of people with neuropathic pain show a distinct pattern: more slow theta waves, fewer alpha waves, and more fast, high beta waves,” Prof. Gustin says. 

“We believe these changes interfere with how the thalamus talks to other parts of the brain, especially the sensory motor cortex, which registers pain.

“I wondered, can we develop a treatment that directly targets and normalises these abnormal waves?”

The challenge was taken up by an interdisciplinary team at UNSW Science and Neuroscience Research Australia (NeuRA), led by Prof. Gustin and Dr Hesam-Shariati, and resulted in PainWaive.

The four participants in its first clinical trial received a kit with a headset and a tablet preloaded with the game app, which includes directions for its use. They were also given tips for different mental strategies, like relaxing or focusing on happy memories, to help bring their brain activity into a more “normal” state.

The user data, meanwhile, was uploaded to the research team for remote monitoring.

“After just a couple of Zoom sessions, participants were able to run the treatment entirely on their own,” says Dr Hesam-Shariati.

“Participants felt empowered to manage their pain in their own environment. That’s a huge part of what makes this special.”

Initially, Dr Hesam-Shariati says, the team planned to use existing commercial EEG systems, but they were either too expensive or didn’t meet the quality needed to deliver the project. Instead, they developed their own.

“Everything except the open-source EEG board was built in-house,” says Dr Hesam-Shariati. “And soon, even that will be replaced by a custom-designed board.”

Thanks to 3D printing, Prof. Gustin says, the team has cut the cost of each headset to around $300 – a fraction of the $1000 to $20 000 price tags of existing systems.

The headset uses a saline-based wet electrode system to improve signal quality and targets the sensorimotor cortex.

“We’ve worked closely with patients to ensure the headset is lightweight, comfortable, and user-friendly,” says Prof. Gustin.

“Owning the technology offers us the potential to one day offer PainWaive as a truly affordable, accessible solution for at-home pain management, especially for those with limited access to traditional treatments.”

The team is currently focussed on a randomised controlled trial of the PainWaive technology, aiming to recruit 224 people with nerve pain following spinal cord injury. 

It’s part of more than a dozen active collaborations between UNSW Science and the Centre for Pain IMPACT at NeuRA, all building on Prof. Gustin’s foundational research into the brain. 

Among these is a clinical trial of an eHealth therapy, called Pain and Emotion Therapy, that was shown to reduce chronic pain by retraining the brain to process emotions more effectively.

Another major project, Project Avatar, is inspired by Prof Gustin’s discovery that half of people with complete spinal cord injuries still have touch signals reaching the brain – though the brain can’t identify them. 

The trial uses immersive virtual reality and real-world touch stimulation to help the brain relearn how to feel.

“Many of our team are clinician-scientists, and we’re focused on developing practical treatments that can be integrated into the healthcare system,” says Prof Gustin.

“It’s incredibly inspiring to see results that help unlock the brain’s potential to heal itself and bring back hope to people living with pain.” 

The researchers are now calling for participants to register their interest in two upcoming trials of the neuromodulation technology: The Spinal Pain Trial, investigating its potential to reduce chronic spinal pain, and the StoPain Trial, exploring its use in treating chronic neuropathic pain in people with a spinal cord injury.

Source: University of New South Wales

Categories : PaediatricsTags : Leave a comment

Singing to Babies Improves Their Mood

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Photo by William Fortunato on Pexels

Around the world and across cultures, singing to babies seems to come instinctively to caregivers. Now, new findings published in Child Development support that singing is an easy, safe, and free way to help improve the mental well-being of infants. Because improved mood in infancy is associated with a greater quality of life for both parents and babies, this in turn has benefits for the health of the entire family, the researchers say. The study also helps explain why musical behaviours may have evolved in parents.

“Singing is something that anyone can do, and most families are already doing,” says Eun Cho, DMA, postdoctoral researcher at the Yale Child Study Center, and co-first author of the study. “We show that this simple practice can lead to real health benefits for babies.”

“We don’t always need to be focusing on expensive, complicated interventions when there are others that are just as effective and easy to adopt,” adds Lidya Yurdum, a PhD student in psychology at the University of Amsterdam, affiliated with the Child Study Center, and co-first author.

Increased singing improves infants’ moods

The new study included 110 parents and their babies, most of whom were under the age of 4 months. The researchers randomly assigned the parents into two groups, encouraging one group to sing to their infants more frequently by teaching the parents new songs, providing karaoke-style instructional videos and infant-friendly songbooks, and sending weekly newsletters offering ideas for incorporating music into daily routines.

For four weeks, these parents received surveys on their smartphones at random times throughout the day. Parents answered questions related to infant mood, fussiness, time spent soothing, caregiver mood, and frequency of musical behavior. For instance, parents were asked to rate how positive or negative their baby’s mood was within the last two to three hours before receiving the survey. The 56 parents in the control group also received an identical intervention in the four weeks following the initial experiment.

The researchers found that parents were successfully able to increase the amount of time they spent singing to their babies. “When you ask parents to sing more and provide them with very basic tools to help them in that journey, it’s something that comes very naturally to them,” says Yurdum.

Not only did the parents sing more frequently, but they also chose to use music especially in one context in particular: calming their infants when they were fussy. “We didn’t say to parents, ‘We think you should sing to your baby when she’s fussy,’ but that’s what they did,” says Samuel Mehr, EdD, an adjunct associate professor at the Child Study Center, and director of The Music Lab. Mehr is also the study’s principal investigator. “Parents intuitively gravitate toward music as a tool for managing infants’ emotions, because they quickly learn how effective singing is at calming a fussy baby.”

Most surprisingly, the responses to the survey showed that increased singing led to a measurable improvement in infants’ moods overall, compared to those in the control group – in other words, parents who sang more rated their babies’ moods as significantly higher. Importantly, improved mood was found in general, not just as an immediate response to music.

While singing did not significantly impact caregivers’ moods in this study, Mehr believes that there could be follow-on effects on health in young families. “Every parent knows that the mood of an infant affects everyone around that infant,” says Mehr. “If improvements to infant mood persist over time, they may well generalize to other health outcomes.”

Follow-up study to further explore singing’s benefits

The team believes that the benefits of singing may be even stronger than the current study shows. “Even before our intervention, these participating families were particularly musical,” Yurdum explains. “Despite that, and despite only four weeks of the intervention, we saw benefits. That suggests that the strength of singing to your babies would likely be even stronger in a family that does not already rely on music as a way of soothing their infants.”

The Child Study Center researchers are currently enrolling parents and babies under 4 months old in a follow-up study, “Together We Grow,” which will investigate the impact of infant-directed singing over an eight-month period.

Although the researchers did not see an improvement in caregiver mood within four weeks, they are intrigued to see if singing can help alleviate stress or conditions such as postpartum depression in the long term. They are also interested in exploring whether singing might have benefits beyond mood in infants, such as improved sleep.

Previous work from The Music Lab has shown that infant-directed music is universal in humans, and that humans can even infer context of songs – such as whether it is for dancing or a lullaby – in foreign languages and from other cultures. For Mehr, the new findings make sense in light of these basic science results. “Our understanding of the evolutionary functions of music points to a role of music in communication,” says Mehr. “Parents send babies a clear signal in their lullabies: I’m close by, I hear you, I’m looking out for you – so things can’t be all that bad.”

The babies, apparently, are listening.

Source: Yale University

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Researchers Spot Chimpanzees Using Medicinal Leaves to Perform First Aid

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Social grooming between two chimpanzees in the Budongo Forest. Photograph by Dr Elodie Freymann.

Researchers monitoring chimpanzee communities in the Budongo Forest, Uganda, noticed that individuals were helping each other with wound care and hygiene. Some of the chimpanzees even used fresh, chewed leaves from plants known for their traditional medicinal uses and bioactive properties to treat their own and their companions’ wounds. Remarkably, they helped individuals they were genetically related to and individuals they weren’t, despite the potential risk from being exposed to pathogens. Researchers believe these findings could help us understand the cognitive and social foundations of healthcare. 

Researchers studying chimpanzees in Budongo Forest, Uganda, have observed that these primates don’t just treat their own injuries, but care for others, too – information which could shed light on how our ancestors first began treating wounds and using medicines. Although chimpanzees elsewhere have been observed helping other community members with medical problems, the persistent presence of this behaviour in Budongo could suggest that medical care among chimpanzees is much more widespread than we realised, and not confined to care for close relatives.  

“Our research helps illuminate the evolutionary roots of human medicine and healthcare systems,” said Dr Elodie Freymann, research affiliate at the School of Anthropology and Museum Ethnography, Oxford University, first author of the article in Frontiers in Ecology and Evolution. “By documenting how chimpanzees identify and utilise medicinal plants and provide care to others, we gain insight into the cognitive and social foundations of human healthcare behaviours.” 

The researchers studied two communities of chimpanzees in the Budongo Forest – Sonso and Waibira. Like all chimpanzees, members of these communities are vulnerable to injuries, whether caused by fights, accidents, or snares set by humans. About 40% of all individuals in Sonso have been seen with snare injuries. 

The researchers spent four months observing each community, as well as drawing on video evidence from the Great Ape Dictionary database, logbooks containing decades of observational data, and a survey of other scientists who had witnessed chimpanzees treating illness or injury. Any plants chimpanzees were seen using for external care were identified; several turned out to have chemical properties which could improve wound healing and relevant traditional medicine uses. 

During their direct observational periods, the researchers recorded 12 injuries in Sonso, all of which were likely caused by within-group conflicts. In Waibira, five chimpanzees were injured – one female by a snare, and four males in fights. The researchers also identified more cases of care in Sonso than in Waibira. 

“This likely stems from several factors, including possible differences in social hierarchy stability or greater observation opportunities in the more thoroughly habituated Sonso community,” said Freymann. 

The researchers documented 41 cases of care overall: seven cases of care for others – prosocial care – and 34 cases of self-care. These cases often included several different care behaviours, which might be treating different aspects of a wound, or might reflect a chimpanzee’s personal preferences.  

“Chimpanzee wound care encompasses several techniques: direct wound licking, which removes debris and potentially applies antimicrobial compounds in saliva; finger licking followed by wound pressing; leaf-dabbing; and chewing plant materials and applying them directly to wounds,” said Freymann. “All chimpanzees mentioned in our tables showed recovery from wounds, though of course we don’t know what the outcome would have been had they not done anything about their injuries.  

“We also documented hygiene behaviours, including the cleaning of genitals with leaves after mating and wiping the anus with leaves after defecation – practices that may help prevent infections.” 

Of the seven instances of prosocial care, the researchers found four cases of wound treatment, two cases of snare removal assistance, and one case where a chimpanzee helped another with hygiene. Care wasn’t preferentially given by, or provided to, one sex or age group. On four occasions, care was given to genetically unrelated individuals.  

“These behaviours add to the evidence from other sites that chimpanzees appear to recognise need or suffering in others and take deliberate action to alleviate it, even when there’s no direct genetic advantage,” said Freymann. 

The researchers call for more research into the social and ecological contexts in which care takes place, and which individuals give and receive care. One possibility is that the high risk of injury and death which Budongo chimpanzees all face from snares could increase the likelihood that these chimpanzees care for each other’s wounds, but more data is needed to explore this.  

“Our study has a few methodological limitations,” cautioned Freymann. “The difference in habituation between the Sonso and Waibira communities creates an observation bias, particularly for rare behaviours like prosocial healthcare. While we documented plants used in healthcare contexts, further pharmacological analyses are needed to confirm their specific medicinal properties and efficacy. Also, the relative rarity of prosocial healthcare makes it challenging to identify patterns regarding when and why such care is provided or withheld. These limitations highlight directions for future research in this emerging field.” 

Source: Oxford University

Categories : NeurologyTags : Leave a comment

Hormone Supplementation in Rhesus Monkeys Points to Potential Autism Treatment

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Photo by Peter Burdon on Unsplash

For years, Florida Tech’s Catherine Talbot, assistant professor of psychology, has worked to understand the sociality of male rhesus monkeys and how low-social monkeys can serve as a model for humans with autism. Her most recent findings show that replenishing a deficient hormone, vasopressin, helped the monkeys become more social without increasing their aggression – a discovery that could change autism treatment.

Currently, the Centers for Disease Control and Prevention report that one in 36 children in the United States is affected by autism spectrum disorder (ASD). That’s an increase from one in 44 children reported in 2018. Two FDA-approved treatments currently exist, Talbot said, but they only address associated symptoms, not the root of ASD. The boost in both prevalence and awareness of the disorder prompts the following question: What is the cause?

Some rhesus monkeys are naturally low-social, meaning they demonstrate poor social cognitive skills, while others are highly social. Their individual variation in sociality is comparable to how human sociality varies, ranging from people we consider social butterflies to those who are not interested in social interactions, similar to some people diagnosed with ASD, Talbot said. Her goal has been to understand how variations in biology and behaviour influence social cognition.

In their paper published in the journal PNAS, Talbot and researchers with Stanford, the University of California, Davis and the California National Primate Research Center explored vasopressin, a hormone that is known to contribute to mammalian social behaviour, as a potential therapeutic treatment that may ultimately help people with autism better function in society. Previous work from this research group found that vasopressin levels are lower in their low-social rhesus monkey model, as well as in a select group of people with ASD.

Previous studies testing vasopressin in rodents found that increased hormone levels caused more aggression. As a result, researchers warned against administering vasopressin as treatment, Talbot said. However, she argued that in those studies, vasopressin induced aggression in contexts where aggression is the socially appropriate response, such as guarding mates in their home territory, so the hormone may promote species-typical behaviour.

She also noted that the previous studies tested vasopressin in “neurotypical” rodents, as opposed to animals with low-social tendencies.

“It may be that individuals with the lowest levels of vasopressin may benefit the most from it – that is the step forward toward precision medicine that we now need to study,” Talbot said.

In her latest paper, Talbot and her co-authors tested how low-social monkeys, with low vasopressin levels and high autistic-like trait burden, responded to vasopressin supplementation to make up for their natural deficiency. They administered the hormone through a nebulizer, which the monkeys could opt into. For a few minutes each week, the monkeys voluntarily held their face up to a nebulizer to receive their dose while sipping white grape juice – a favorite among the monkeys, Talbot said.

After administering the hormone and verifying that it increased vasopressin levels in the central nervous system, the researchers wanted to see how the monkeys responded to both affiliative and aggressive stimuli by showing them videos depicting these behaviors. They also compared their ability to recognize and remember new objects and faces, which is another important social skill.

They found that normally low-social monkeys do not respond to social communication and were better at recognizing and remembering objects compared to faces, similar to some humans diagnosed with ASD. When the monkeys were given vasopressin, they began reciprocating affiliative, pro-social behaviors, but not aggression. It also improved their facial recognition memory, making it equivalent to their recognition memory of objects.

In other words, vasopressin “rescued” low-social monkeys’ ability to respond prosocially to others and to remember new faces. The treatment was successful – vasopressin selectively improved the social cognition of these low-social monkeys.

“It was really exciting to see this come to fruition after pouring so much work into this project and overcoming so many challenges,” Talbot said of her findings.

One of Talbot’s co-authors has already begun translating this work to cohorts of autism patients. She expects more clinical trials to follow.

In the immediate future, Talbot is examining how other, more complex social cognitive abilities like theory of mind – the ability to take the perspective of another – may differ in low-social monkeys compared to more social monkeys and how this relates to their underlying biology. Beyond that, Talbot hopes that they can target young monkeys who are “at-risk” of developing social deficits related to autism for vasopressin treatment to see if early intervention might help change their developmental trajectory and eventually translate this therapy to targeted human trials. 

Source: Florida Tech