Publisher Health

All it takes is three consecutive nights of sleep loss to cause your mental and physical well-being to greatly deteriorate. A new study published in Annals of Behavioral Medicine looked at the consequences of sleeping fewer than six hours for eight consecutive nights — the minimum duration of sleep that experts say is necessary to support optimal health in average adults.
Lead author Soomi Lee, assistant professor in the School of Aging Studies at the University of South Florida, found the biggest jump in symptoms appeared after just one night of sleep loss. The number of mental and physical problems steadily got worse, peaking on day three. At that point, research shows the human body got relatively used to repeated sleep loss. But that all changed on day six, when participants reported that the severity of physical symptoms was at its worst.
“Many of us think that we can pay our sleep debt on weekends and be more productive on weekdays,” Lee said. “However, results from this study show that having just one night of sleep loss can significantly impair your daily functioning.”
Data provided by the Midlife in the United States study included nearly 2,000 middle-aged adults who were relatively healthy and well-educated. Among them, 42% had at least one night of sleep loss, sleeping 1 ½ fewer hours than their typical routines. They recorded their mental and physical behaviors in a diary for eight consecutive days, allowing researchers to review how sleep loss causes wear and tear on the body.
Participants reported a pile-up of angry, nervous, lonely, irritable and frustrated feelings as a result of sleep loss. They also experienced more physical symptoms, such as upper respiratory issues, aches, gastrointestinal problems and other health concerns. These negative feelings and symptoms were continuously elevated throughout consecutive sleep loss days and didn’t return to baseline levels unless they had a night sleep of more than six hours.
About one-third of U.S. adults sleep less than six hours per night. Lee says once that becomes a habit, it’s increasingly difficult for your body to fully recover from lack of sleep, continuing the vicious cycle of worsening daily well-being, which could impact one professionally. A previous study led by Lee found losing just 16 minutes of sleep could impact job performance. Her previous findings also show that minor sleep loss can decrease daily mindfulness, which is a critical recourse for managing stress and maintaining healthy routines.
Lee says the best way to maintain a strong daily performance is to set aside more than six hours to sleep every night.
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Chromosomal instability is a feature of solid tumours such as carcinoma. Likewise, cellular senescence is a process that is highly related to cellular ageing and its link to cancer is becoming increasingly clear. Scientists led by ICREA researcher Dr. Marco Milán at IRB Barcelona have revealed the link between chromosomal instability and cellular senescence.
“Chromosomal instability and senescence are two characteristics common to most tumours, and yet it was not known how one related to the other. Our studies indicate that senescence may be one of the intermediate links between chromosomal alterations and cancer,” says Dr. Milan, head of the Development and Growth Control laboratory at IRB Barcelona.
“The behaviour we saw in cells with chromosomal instability made us think that they could be senescent cells and indeed that was the case!” says Dr. Jery Joy, first author of the article published in Developmental Cell.
The study has been conducted on the fly Drosophila, an animal model commonly used in biomedicine, and the mechanisms described may help to understand the contribution of chromosomal instability and senescence to cancer, and facilitate the identification of possible therapeutic targets.
Reversing the effects of chromosomal instability
The researchers from the Development and Growth Control lab have shown that, in an epithelial tissue with high levels of chromosomal instability, those cells with an altered balance of chromosome number detach from their neighbouring cells and enter senescence. Senescent cells are characterised by a permanently halted cell cycle and by the secretion of a large number of proteins. This abnormal secretion of proteins alters the surrounding tissue, alerting the immune system and causing inflammation.

The death of cells is well regulated. If it occurs too much, it can cause degenerative diseases. Too little, and cells can become tumours. Mitochondria, the power plants of cells, play a role in this programmed cell death. Scientists from the University of Groningen (the Netherlands) and the University of Pittsburgh (U.S.) have obtained new insights in how mitochondria receive the signal to self-destruct. Their results were published in the Journal of Molecular Biology.
How does a cell kill itself? The details of this process are still unclear. Patrick van der Wel, associate professor of Solid-State NMR Spectroscopy at the University of Groningen, is working together with colleagues at the University of Pittsburgh to see how cell death is initiated on a molecular level. ‘The membranes of mitochondria play a key role’, he explains. Cardiolipin, a special type of membrane lipid, acts as an important signal. ‘If it gets reshuffled inside the membrane and oxidized, this can trigger cell death.’
Unfolding
Another factor is the small protein cytochrome c. This plays an important role in energy production by mitochondria, but it can also bind to cardiolipin. ‘We believe it may control oxidation of the cardiolipin, which is part of the initiation process for programmed cell death’, explains Van der Wel. It was previously thought that the unfolding of cytochrome c on the cell membrane was important, as this allows it to oxidize cardiolipin, a step that triggers cell death. However, in a previous paper, Van der Wel and his U.S. colleagues published evidence that cytochrome c is not unfolded.
‘In our new study, we have looked in even more detail at the interaction between cytochrome c and the mitochondrial membrane’, says Van der Wel. They used solid-state NMR to detect the position and the status of all 105 amino acids in the protein. The NMR signals of two connected carbon atoms in an amino acid depend on how they interact with other atoms in the molecule. Therefore, the measured spectrum of the carbon atoms can show in which amino acid they are located. Such information can be used to get an idea of the protein’s structure, even if it is not well ordered.
Discrepancy
‘Furthermore, with this technique, an amino acid is only visible in a fixed part of the protein structure. If it is in an unfolded part, it can move more freely and becomes invisible.’ Thus, solid-state NMR spectroscopy can show which parts of the protein are folded or unfolded. ‘What we saw is that cytochrome c is not fully unfolded when attached to the cardiolipins in the mitochondrial membrane.’
Proteins fold in a particular order: the first fold induces a second, third, and so on. ‘These steps are called foldons. What we saw in our experiments is that when binding to the membrane, different foldons in cytochrome c unfold at different stages. And some parts do not unfold at all.’ This finding explains the discrepancy between the results of Van der Wel and his colleagues and those of previous papers: these studies were too coarse-grained to be able to clearly see which parts of cytochrome c were still folded.
Drugs
These results are interesting, as they provide fundamental insight into how programmed cell death is regulated at the molecular level. ‘They add to our previous idea that oxidation of cardiolipin by cytochrome c is a very well-controlled, specific process.’ Furthermore, knowing which parts of the protein unfold means that it will be possible to develop drugs that stabilize or destabilize them. Such drugs could be used as regulators that could increase or reduce programmed cell death. Van der Wel: ‘We would like to use our data to construct a realistic computer model for this protein interaction so that it is possible to design these drugs in silico.’
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Scientists at the University of Leeds have developed an approach that could help in the design of a new generation of synthetic biomaterials made from proteins.
The biomaterials could eventually have applications in joint repair or wound healing as well as other fields of healthcare and food production.
But one of the fundamental challenges is to control and fine tune the way protein building blocks assemble into complex protein networks that form the basis of biomaterials.
Scientists at Leeds are investigating how changes to the structure and mechanics of individual protein building blocks — changes at the nanoscale — can alter the structure and mechanics of the biomaterial at a macro level while preserving the biological function of the protein network.
In a paper published by the scientific journal ACS Nano, the researchers report that they were able to alter the structure of a protein network by removing a specific chemical bond in the protein building blocks. They called these bonds the “protein staples.”
With the protein staples removed, the individual protein molecules unfolded more easily when they connect together and assemble into a network. This resulted in a network with regions of folded protein connected by regions containing the unfolded protein resulting in very different mechanical properties for the biomaterial.

“It’s Never Too Late” is a new series that tells the stories of people who decide to pursue their dreams on their own terms.Vijaya Srivastava’s first 68 years had been resolutely land-based. She walked the Berkeley Hills in the San Francisco Bay Area, spent time with her young grandchildren, volunteered at the library. None of this required submersion in water, which suited her fine, what with water being terrifying. Fear of drowning was a big issue.Growing up in India, she never had access to swimming pools. By the time she moved to the United States, the idea of backstroking to and fro simply didn’t occur to her. Then one day her physician mentioned that regular laps would improve her health.“I can’t swim,” Ms. Srivastava, now 72, confessed. She’d never even put her face underwater.“Have you heard of lessons?” the physician asked.“At my age?”“Why not?”What followed might have been a long period of pondering that question. That’s not what happened. (The following interview has been edited and condensed.)Growing up in India, Ms. Srivastava, now 72, never had access to swimming pools.Aubrey Trinnaman for The New York TimesQ: What were your first steps?A: The first thing I did was ask a neighbor if she wanted to take lessons together. We hired a high school kid, from Albany High. She had lifeguard training — I liked that.“Have you ever trained a senior?” we asked. She said no. OK.We started lessons three days a week.Once I decided to learn, that was it. I went to the pool on the days between lessons. I started to dream about swimming. I’d wake up excited. When I couldn’t get to sleep, I would swim in bed. My husband would say, “What’s going on? This isn’t a pool …”I also bought many bathing suits — I thought one of them might be lucky. Later I realized you don’t need 10. I donated quite a few.Did you do any research into swimming?After my first lesson, I started to Google. At first I would just watch anything on YouTube had about how to swim. That got confusing. Later my daughter told me about Total Immersion Swimming videos. There’s a guy who gets into the physics of swimming, that helped me a lot.Also my grandkids would go underwater and watch my breaststroke, or sit in the hot tub and give me thumbs up or thumbs down.What were the biggest challenges?Being petrified. Nothing had ever happened to me to make me scared. It was just knowing that I could drown. For the longest time I stayed in the shallow end, four feet. I prayed before every lesson.And not having enough stamina. My arms and legs weren’t ready. After half an hour I was so tired.Ms. Srivastava began to swim in her late 60s.Aubrey Trinnaman for The New York TimesShe was prompted to learn by a doctor who suggested it as exercise.Aubrey Trinnaman for The New York TimesWas there a moment when it all clicked?After a few months, the instructor started telling me, “It’s time to go to the other end.” I kept saying, “I’m not ready.” She said, “You are.”Finally I decided if I don’t try, it’s never going to happen. The instructor said she’d be next to me the whole time.“But you’re so tiny!” I told her. She promised she wouldn’t let me drown.So I started swimming. When I hit the six-feet marker — I’m 5 foot, 4 inches — I knew there was no turning around. Also, I didn’t know how to turn around.Finally I made it to the other side. My neighbors from the condominium were over in the hot tub. They’d been watching me struggle for the last few months, and now they all stood up and clapped for me.I didn’t wave back until I caught my breath and swam back to the shallow end. There’s no way I was taking my hand off the wall in the eight-foot end.What would you have done differently when you started?There’s not much I would do differently. Maybe start earlier.How has your new pursuit changed your life?When we talk about it — my nephews, my children — they sound so proud of me. Not too many people my age, or in my family, swim. It’s a good feeling that I’ve done this. I talk to my family back home in India. My brother can’t believe it.What’s next?I was talking to a friend about learning how to dance — maybe we could take dance lessons?What would you tell people who feel stuck and want to make a change?I found it good to have my neighbor swimming with me. We would motivate each other. If I was tired that day, she would say let’s just go for 20 minutes. Twenty minutes turns into half an hour.“I still take a break after laps,” she said. “My next goal is to do it continuously, without taking a break. I’ll get there.”Aubrey Trinnaman for The New York TimesHas your experience made you a different person?Swimming a pool length for the first time at the age of 68 — that will always stay with me. Last Friday I swam 20 laps! It took me 52 minutes. I still take a break after laps. My next goal is to do it continuously, without taking a break. I’ll get there.What do you wish you had known earlier about being fulfilled?I have a very good friend who told me to know your body, know yourself — what makes you happy, healthy, angry. That always stayed with me. That helped me a lot.But there’s not much in my life I would change. If you’re relaxed in your mind, and happy, that brings you health. You don’t need too many things in life.What lessons can people learn from your experience?Don’t give yourself an option to give up. I never thought about quitting. If I invest mentally, I don’t quit.We’re looking for people who decide that it’s never too late to switch gears, change their life and pursue dreams. Should we talk to you or someone you know? Share your story here.

A research collaboration based in Kumamoto University, Japan has discovered that muscles and the resident stem cells (satellite cells) responsible for muscle regeneration retain memory of their location in the body. This positional memory was found to be based on the expression pattern of the homeobox (Hox) gene cluster, which is responsible for shaping the body during fetal life. These findings are expected to provide clues to elucidate the pathogenesis of muscle diseases such as muscular dystrophy, in which the position of muscle vulnerability varies depending on the type of muscle, and to help develop regenerative medicine based on positional memory.
There are various types of the intractable muscle disease muscular dystrophy and each type has a different symptom location. Similarly, age-related muscle fragility (sarcopenia) does not occur evenly throughout the body. The physical location of the symptoms of these diseases cannot be explained by differences in muscle fiber types or physical activity patterns alone, and requires a new perspective to elucidate their respective pathogeneses.
The developmental origin of cells that form muscles differ in the fetal stage. For example, most of the craniofacial muscles originate from the cranial mesoderm, while the limb muscles originate from the body segments. Development of limb and craniofacial muscles in the fetal period involves specific molecular mechanisms that depends on their origin. However, differences in the properties of mature skeletal muscle depending on body position after birth have not been fully discussed. Thus, a research collaboration worked to visualize the body’s positional information by studying the epigenomic state and gene expression patterns of skeletal muscle and the muscle stem cells responsible for regeneration.
Using skeletal muscle and associated muscle stem cells isolated from the heads and hind limbs of adult mice, researchers investigated positional specificity at the epigenomic level using DNA methylome analysis. They found characteristic differences in the DNA methylation status at the homeobox (Hox) loci. Among four regions, A to D, the Hox-A locus in particular had an overall DNA hypermethylation state in hindlimb skeletal muscle and muscle stem cells compared to the head. Additionally, both skeletal muscle and muscle stem cells in the hind limbs showed high expression of the Hox-A gene. Many of these Hox-A genes reflected expression patterns in the fetal period. These findings suggest that skeletal muscle and muscle stem cells remember positional information during fetal life, and that epigenomic regulation by DNA methylation may be involved in positional memory.
The researchers then focused on the Hoxa10 gene, which was highly expressed only in the limb muscles. When hindlimb-derived muscle stem cells expressing Hoxa10 were isolated and transplanted into craniofacial muscles that do not express Hoxa10, Hoxa10 gene expression became detectable in the craniofacial muscles. In other words, hindlimb-derived muscle stem cells were able to innervate the craniofacial muscle with strong retention of positional memory even after ectopic transplantation.
They then created mice lacking the Hoxa10 gene in muscle stem cells to analyze its function. A Hoxa10 deficiency severely impaired the regeneration of hindlimb muscles but had no effect on craniofacial muscle regeneration. A detailed investigation of the mechanism behind the hindlimb muscle regeneration disorder revealed that it is caused by genomic instability due to abnormal chromosome distribution during muscle stem cell division. Furthermore, analysis of human head and leg muscle stem cells also showed that only leg muscle cells expressed the HOX-A gene and that its inhibition resulted in abnormal cell division, confirming that muscle cell positional memory is retained in humans and mice.
This research suggest that the positional memory of muscle stem cells based on the position-specific distribution of Hox gene expression may determine the position-specific properties of skeletal muscle, rather than merely persisting from fetal life.
“In the future, we expect that the functional aspects of muscle stem cell positional memory will lead to the clarification of the mechanisms that lead to location-specificity of symptoms that are observed in various muscle diseases like muscular dystrophy,” said Associate Professor Yusuke Ono, who led the study. “In addition, ectopic transplantation experiments, in which muscle stem cells are transplanted to a location different from where they were harvested, have shown that they maintain positional memory and regenerate. From a different perspective, skeletal muscles regenerated from xenotransplantation may not possess their original positional information which may impair their normal function. There has been rapid progress recently in the differentiation of iPS cells into various progenitor cells and the development of mass culture techniques, but the location of induced progenitor cells has not been considered. In the future, our group will attempt to develop regenerative therapy applications for muscle diseases by artificially controlling the positional memory of cells and by utilizing the properties of cells with positional memory in the right places.”
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A new international study has found that the key properties of the spikes of SARS-CoV-2 virus which causes COVID-19 are consistent with those of several laboratory-developed protein spikes, designed to mimic the infectious virus.
A central component in designing serological tests and vaccines to protect against COVID-19 is the manufacture of protein “spikes.” These recombinant spikes closely mimic those sticking out of surface of the infectious virus and trigger the body’s immune system into action.
Laboratory manufactured spikes are also used for serological testing (also referred to as antibody testing) and as research reagents. The findings show how that viral spike manufactured through different methods in laboratories across the globe are highly similar and provide reassurance that the spike can be robustly manufactured with minimal variations between laboratories.
The spikes on the SARS-CoV-2 virus are coated in sugars, known as glycans, which they use to disguise themselves from the human immune system. The abundance of these glycans has the potential to create significant discrepancies between studies that use different recombinant spikes.
In this new study, published in the journal Biochemistry, the research team studied the glycan coatings on recombinant spikes developed in five laboratories around the world and compared them to those on the spikes of the infectious virus.
“The speed at which scientific community has moved to tackle the COVID-19 pandemic has put considerable pressure on laboratories around the world to validate their findings quickly,” Explained Max Crispin, Professor of Glycobiology at the University of Southampton, who led the study. “Over the last year we have seen vaccines developed around the world at an unprecedented rate and the rapid development, and validation, of recombinant proteins have been fundamental to that success story,” he continued.
In April 2020, Professor Crispin and his team from the University of Southampton mapped the glycan coating of the SARS-CoV-2 spike for the first time. In the present study, they extend their analysis to examine recombinant spike developed in laboratories at the Amsterdam University Medical Centre, Harvard Medical School, the University of Oxford, and the Swiss company ExcellGene. All the different batches of spike protein were shown to mimic key features of the glycosylation of virions analysed at Tsinghua University, China.
The study also used computational methods to examine the protein features that were shaping some of the glycosylation features that were seen across all the samples. Dr. Peter Bond, Senior Principal Investigator at the Bioinformatics Institute of the Agency for Science, Technology and Research (A*STAR), Singapore, who led the computational work said, “Our modelling enabled us to shed light on how the protein influences the structure of the glycans and why the glycosylation was so consistent. This predictive approach could also be of potential value in therapeutics development against new variants or other emerging viruses.”
“The ability to produce mimics of the SARS-CoV-2 spike protein with high fidelity at many different laboratories, all of which recapitulate the glycan signatures of the authentic virus, is of significant benefit for vaccine design, antibody testing and drug discovery” concluded Professor Crispin.
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A new report that could help improve how immersive technologies such as Virtual Reality (VR) and Augmented Reality (AR) are used in healthcare education and training has been published with significant input from the University of Huddersfield.
Professor David Peebles, Director of the University’s Centre for Cognition and Neuroscience, and Huddersfield PhD graduate Matthew Pears contributed to the report — ‘Immersive technologies in healthcare training and education: Three principles for progress’ — recently published by the University of Leeds with input from range of academics, technologists and health professionals.
The principles have also been expanded upon in a letter to the prestigious journal BMJ Simulation and Technology Enhanced Learning.
The Huddersfield contribution to the report stems from research conducted over several years, which involved another former Huddersfield PhD researcher, Yeshwanth Pulijala, and Professor Eunice Ma, now with Falmouth University.
“Yeshwanth had an interest in technology and education, and in using VR for dentistry training. Matthew was looking at soft skills and situation awareness, which could be applied to investigating how dentists were able to keep a track of what was going on around them. They were similar subjects, although with different emphases, and so it seemed a natural area for collaboration.”
With only a relatively small number of dental schools in the UK, the quartet visited seven dental schools in India in early 2017, with support from travel grants from Santander Bank, to test their VR-based training materials on students. The experience gained from that visit contributed to both researchers’ PhDs, and ultimately led to the involvement of Professor Peebles and Matthew Pears in the new report.
The report argues for greater standardisation of how to use immersive technologies in healthcare training and education. As Professor Peebles explains, “It’s about developing a set of principles and guidelines for the use of immersive technology in medical treatment. Immersive technology is becoming increasingly popular and, as the technology is advancing, it’s becoming clear that there is great potential to make training more accessible and effective.
“It is important, however, that research is driven by the needs of the user and existing evidence rather than the technology. Rather than thinking ‘we have a new bit of VR or AR kit, what can we do with it?’, we should be looking at the problem that needs solving — what are the learning needs, so how do we use technology to solve it?
“Developing immersive training materials can be very time-consuming and difficult to evaluate properly. Getting surgeons and medical students to take time out to test your VR training is challenging. In our case we were lucky to have a surgeon, Professor Ashraf Ayoub, a Professor of Oral and Maxillofacial Surgery at the University of Glasgow, who granted us permission to film a surgical procedure that was then transformed into a 3D environment to train students about situation awareness while in the operating theatre.”
Professor Peebles hopes the work so far will provide a basis for more investigations that could help get the most from the potential that VR and immersive technology have to offer.
“Conducting these kinds of studies is difficult to do well, in particular getting sufficient quantitative data that allows you to rigorously evaluate them. “As the report recommends, more collaboration is required to pool technological and intellectual resources, to try to develop a set of standards and a community that works together to boost and improve research in this area.”
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Cleft lip and palate is one of the most common congenital malformations. Its causes are mainly genetic. However, it is still largely unknown exactly which genes are affected. A new international study led by the University of Bonn now provides new insights. The results are published in the journal Human Genetics and Genomics Advances, but are already available online.
The researchers from the Institute of Human Genetics at the University Hospital Bonn combined various data sources in their work. In the course of their research, they discovered five new regions in the human genome in which variations in the DNA sequence are associated with an increased risk of malformation. A total of 45 such risk regions are now known. For some of them, the researchers were also able to show which genes are affected by these changes. “Our results provide new insights into the development of the disease, but also into the development of the face in the early embryo as a whole,” explains Dr. Kerstin Ludwig.
Ludwig leads an Emmy Noether junior research group at the Institute of Human Genetics at the University Hospital Bonn, which focuses on the genetic causes of cleft lip and palate. The average contribution of genes to this frequent malformation is estimated at more than 90 percent. “The genetic contribution is complex,” Ludwig says. “That means there is not just one gene, but a whole set of genes that contribute to the malformation.”
Data from previously published genomic studies combined
The blueprint of each individual human being is stored in his or her DNA, a kind of giant lexicon with around three billion letters. People are different, and the contents of their DNA lexicon differ accordingly. However, for people with a cleft lip and palate, at least the passages that have something to do with the disease should be similar. Science makes use of this basic assumption: By comparing the DNA of many thousands of affected individuals at several million sites, researchers can identify genetic regions that result in a higher risk of disease.
A whole series of such “genome-wide association studies” (GWAS) have been published in recent years. “We have now combined data from previously published GWAS,” explains Dr. Julia Welzenbach, a postdoctoral researcher in Ludwig’s group who led the study that has now been published. This makes it possible to find even those changes in DNA that only slightly increase the risk for the malformation and are therefore overlooked in individual studies. “In this way we identified five risk regions that were previously unknown,” Welzenbach says.
However, this does not automatically contribute to a better understanding of the disease: Only about two percent of DNA actually contains genetic information in the sense of direct instructions for building proteins. Science is just beginning to understand what the remaining 98 percent is for. “The 45 risk regions we know about today are all within that 98 percent, which we also call non-coding regions,” Welzenbach explains.
It is now known that part of the non-coding DNA serves to regulate the activity of genes. Some of these DNA regions ensure, for example, that a certain gene is read more frequently or in certain tissues. Such regulatory regions are therefore also called enhancers. Others, however, act as silencers — they switch off certain genes.
Mutations affect regulatory DNA elements
In each cell, only certain genes are active at a given time of development. In other words, there is a cell type- and time-specific pattern of gene activity, and the silencers and enhancers are partly responsible for this. “Some regulatory DNA sequences are now known to act as silencers or enhancers during early facial development of the embryo,” Ludwig says. “We were able to show for some of the genetic changes from the GWAS data that they affect these regulatory sequences, and therefore also show which genes increase or decrease in activity as a result.”
Presumably, each of the 45 risk regions known today alters the effect of an enhancer or silencer. In this way, they disrupt the finely balanced activity pattern of genes that play a role in error-free facial development. And it is this disruption, combined with additional factors, that increase an individual’s risk to get a cleft lip and palate.
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From the bark of a puppy to the patter of rain against the window, our brains receive countless signals every second. Most of the time, we tune out inconsequential cues — the buzz of a fly, the soft rustle of leaves in the tree — and pay attention to important ones — the sound of a car horn, a bang on the door. This allows us to function, navigate and, indeed, survive in the world around us.
The brain’s remarkable ability to sift through this ceaseless flow of information is enabled by an intricate neural network made up of billions of synapses, specialized junctions that regulate signal transmission between and across cells. Some of these junctions inhibit signal transmission, others accelerate it — a millisecond-by-millisecond balancing act which ensures that our brains function with maximum efficiency.
Now a new study by researchers at Harvard Medical School and at the Broad Institute of MIT and Harvard shows that this delicate equilibrium between inhibition and excitation is maintained, at least in part, by a highly specialized subset of microglia — the brain’s resident immune cells, known for their role in fighting infection and cleanup of cellular debris.
The research, conducted in mice and published July 6 in Cell, reveals for the first time that this cadre of specialized immune cells is finely attuned to detecting and engaging exclusively with inhibitory synapses, the junctions that slow down the flow of information from cell to cell.
“We found that specialized immune and neuronal cells engage in important communication during early brain development and form interactions critical to the establishment of balanced brain wiring,” said study first author Emilia Favuzzi, research fellow in neurobiology in the Blavatnik Institute at HMS and a postdoctoral scholar at the Broad.
“Our observations suggest that microglia engage in an act of intricate interplay with specific types of synapses, homing in on them and sculpting the nervous system in a synapse-by-synapse manner,” said study senior investigator Gordon Fishell, professor of neurobiology in the Blavatnik Institute at HMS and group leader in the Stanley Center for Psychiatric Research at the Broad. “This is the first time we have shown that certain types of microglia are recruited to certain types of synapses and engage with them in a very specific way.”
Moreover, the research showed, these cells interact with inhibitory synapses through direct physical contact, a first-of-a-kind observation enabled by advanced imaging techniques that allowed the researchers to observe in real time how cells in the brains of mice engage with one another.