Spit Samples Uncover Genetic Risk Factors For Paediatric Obsessive-compulsive Disorder (Psychiatry)

UCalgary collaboration with SickKids could be a step toward earlier diagnosis and improved treatment for children and youth with OCD

When Sam was 14 years old, his mind was so full of fear, he couldn’t think about anything else.

“I had really bad tendencies,” says Sam, now 17. “I would dehydrate myself to prevent going to the bathroom. I was very picky about things being sanitary. It was getting in the way of everything.”

After school he would shower for up to two hours, using two bars of soap. He would then worry that the books he had brought home weren’t clean enough to bring in the house. Sam says that when things were at their worst, he was diagnosed with obsessive-compulsive disorder (OCD).

Researchers at the University of Calgary and The Hospital for Sick Children (SickKids), in Toronto, have discovered genetic risk factors for OCD that could help pave the way for earlier diagnosis and improved treatment for children and youth.

“Our group made the first finding of a genome-wide significant risk gene relevant to childhood OCD,” says Dr. Paul Arnold, MD, PhD, co-principal investigator, a professor and director of The Mathison Centre for Mental Health Research and Education at the Cumming School of Medicine. “We’ve known that OCD runs in families, but we hadn’t identified and validated specific genetic risks of OCD symptoms in children and youth until now.”

Paul Arnold

The research drew on the Spit for Science study, a research project led by SickKids looking at how genes interact with the environment to impact physical and mental health. Participants from the community were recruited via an innovative research design run out of the Ontario Science Centre, which has generated a diverse sample of 23,000 participants thus far. Participants provide a DNA sample through their saliva, do a cognitive task, and complete questionnaires on their health, lifestyle and behaviours.

Genetic variant in the gene PTPRD linked to greater risk

In this study, saliva samples from over 5,000 children and youth were scanned and compared to participant responses using the Toronto Obsessive-Compulsive Scale (TOCS). The TOCS is a questionnaire used to evaluate obsessive-compulsive traits developed by Dr. Arnold and the team at SickKids. After looking across millions of genetic variants from the saliva samples, the team identified that children and youth with a genetic variant in the gene PTPRD had a greater risk for more obsessive-compulsive traits. The findings were published in Translational Psychiatry on Feb. 3, 2021.

“Discovering the genes involved in OCD is critical to help improve patients’ lives. It is still early days, but our hope is these findings will lead us to understand the causes of OCD, which in turn could help identify people with OCD sooner and develop better treatments,” says Dr. Christie Burton, PhD, lead author and research associate in the Neurosciences and Mental Health program at SickKids.  

Christie Burton, Jennifer Crosbie and Russell Schacha

The research team, which also includes co-principal investigators, Drs. Jennifer Crosbie, PhD, clinical psychologist at SickKids, and Russell Schachar, MD, psychiatrist at SickKids, highlight that a greater understanding of the underlying genetics may eventually be an important complement to clinical assessment and could help guide treatment options in the future.

“OCD can present very differently and at various ages in each individual, adding to the challenge of treatment and diagnosis,” says Crosbie, who is also an associate scientist in the Neurosciences and Mental Health program at SickKids. “Studies like this one are an important step towards developing precision medicine approaches for mental health.”

OCD diagnosis surprised Sam and his family

With therapy and medication, Sam has been able to face his obsessions and compulsions, ride out the anxiety and control his actions. Looking back at his childhood, Sam says he had some OCD tendencies as early as elementary school, but neither he nor his family realized he had a mental illness. The researchers hope that by understanding the genetics of OCD, they can develop better treatments, improve outcomes and diagnose youth like Sam earlier.

“At first I wasn’t sure what to do with the diagnosis, it was very foreign, I didn’t want to perceive myself as having a mental health issue,” says Sam. “But, knowing I have OCD helped me overcome the challenges. With therapy and medication, I’ve stopped OCD from overtaking my life and taken back control of my thoughts.”

Sam is a real teenager, but Sam isn’t his real name. He says due to the stigma around OCD he would prefer to remain anonymous.

This study is supported by the Canadian Institutes of Health Research and SickKids Foundation.

Reference: Burton, C.L., Lemire, M., Xiao, B. et al. Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder. Transl Psychiatry 11, 91 (2021). https://doi.org/10.1038/s41398-020-01121-9

Provided by University of Calgary

USC Stem Cell Study Reveals Neural Stem Cells Age Rapidly (Biology)

Researchers at Keck School of Medicine of USC conduct first-ever study of Abl1 gene’s role in neural stem cell biology and the implications for cognitive decline

In a new study published in Cell Stem Cell, a team led by USC Stem Cell scientist Michael Bonaguidi, PhD, demonstrates that neural stem cells – the stem cells of the nervous system – age rapidly.

“There is chronological aging, and there is biological aging, and they are not the same thing,” said Bonaguidi, an Assistant Professor of Stem Cell Biology and Regenerative Medicine, Gerontology and Biomedical Engineering at the Keck School of Medicine of USC. “We’re interested in the biological aging of neural stem cells, which are particularly vulnerable to the ravages of time. This has implications for the normal cognitive decline that most of us experience as we grow older, as well as for dementia, Alzheimer’s disease, epilepsy and brain injury.”

In the study, first author Albina Ibrayeva, a PhD candidate in the Bonaguidi Lab in the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, joined her colleagues in looking at the brains of young, middle-aged and old mice.

By tracing individual neural stem cells, or NSCs, over the course of several months, they identified “short-term NSCs” that quickly differentiate into more specialized neurons, and “long-term NSCs” that continually divide and replicate themselves to maintain an ongoing reserve of stem cells with the ability to generate many different cell types in the brain. This key population of long-term NSCs divided less often and failed to maintain their numbers as the mice aged.

The scientists next examined thousands of genes in the long-term NSCs, which were dividing less often and had slipped into an inactive state known as quiescence. The gene activity of the quiescent NSCs varied greatly in young versus middle-aged animals. As expected, there were changes in genes that control how long-term NSCs divide, as well as generate new neurons and other brain cells. Remarkably, there were many important changes in gene activity related to biological aging at younger ages than anticipated. These pro-aging genes make it more difficult for cells to repair damage to their DNA, regulate their genetic activity, control inflammation and handle other stresses.

Among the pro-aging genes, the scientists were most intrigued by Abl1, which formed the hub of a network of interrelated genes.

“We were interested in the gene Abl1, because no one has ever studied its role in neural stem cell biology–whether in development or in aging,” said Ibrayeva.

Using an existing, FDA-approved chemotherapy drug called Imatinib, scientists could easily inhibit the activity of the gene Abl1. The scientists gave older mice doses of Imatinib for six days. After the drug blocked the activity of the gene Abl1, the NSCs began to divide more and proliferate in the hippocampus, the part of the brain responsible for learning and memory.

“We’ve succeeded in getting neural stem cells to divide more without depleting, and that’s step one,” said Bonaguidi. “Step two will be to induce these stem cells to make more neurons. Step three will be to demonstrate that these additional neurons actually improve learning and memory. Much work remains to be done, but this study marks exciting progress towards our goal of identifying prescription drugs that could rejuvenate our brains as we grow older.”

Additional co-authors include: Maxwell Bay, Elbert Pu, Lei Peng, Naibo Zhang, Daniel Aaron, Congrui Lin, Galen Resler, and Axel Hidalgo from USC; David Jorg and Benjamin D. Simons from the University of Cambridge; and Heechul Jun and Mi-Hyeon Jang from the Mayo Clinic College of Medicine.

Seventy percent of the research was supported by federal funding from the National Institutes of Health (R00NS080913, R56AG064077, R01AG0585560, and T32HD060549-08), and the remainder was supported by non-federal funding from the Donald E. and Delia B. Baxter Foundation, the L.K. Whittier Foundation, The Eli and Edythe Broad Foundation, the Children’s Hospital Los Angeles TSRI pilot program, a Royal Society E P Abraham Professorship (RP\R1\180165), the Wellcome Trust (098357/Z/12/Z), the American Federation for Aging Research Scholarship for Research in Biology of Aging and the USC Provost’s Research Enhancement Fellowship.

Featured image: Neural stem cell clones in young (green) and old (red) mouse brains. © Albina Ibrayeva/Bonaguidi Lab

Reference: Albina Ibrayeva, Maxwell Bay, Elbert Pu, David J. Jörg, Lei Peng, Heechul Jun, Naibo Zhang, Daniel Aaron, Congrui Lin, Galen Resler, Axel Hidalgo, Mi-Hyeon Jang, Benjamin D. Simons, Michael A. Bonaguidi, Early stem cell aging in the mature brain, Cell Stem Cell, 2021, , ISSN 1934-5909, https://doi.org/10.1016/j.stem.2021.03.018. (https://www.sciencedirect.com/science/article/pii/S1934590921001247)

Provided by Keck School of Medicine of USC

New Brain Proteins Suspected of Causing Depression (Neuroscience)

Can they play a pivotal role in treating the illness, as well?

Using an innovative protein-based approach, researchers at the Atlanta VA Medical Center and nearby Emory University have found genes and corresponding proteins that could point the way to new depression treatments.

“We are very excited to continue to work on these promising targets in our lab but caution that the road leading to new drugs is long and difficult.”

Using a proteome-wide association study (PWAS) that integrated genome-wide association study (GWAS) data with human brain proteomic and genetic data, researchers have identified 19 genes that may lead to depression by altering brain protein levels. They also pinpointed 25 such proteins that offer promise as potential targets for new depression treatments.

The researchers detail their approach and findings in April 2021 in the journal Nature Neuroscience.

Identifying brain proteins that cause depression

Depression is a common condition, but current treatments are ineffective for many people with the mental illness. This research sets the stage for finding new drugs to treat the illness by identifying important gene-protein pairs that likely contribute to the cause of depression and could serve as promising targets for future studies, according to lead researcher Dr. Aliza Wingo, a psychiatrist at the Atlanta VA. She’s also an associate professor at Emory University.

Wingo works with Dr. Thomas Wingo, the first author of the study, at their joint laboratory at the Atlanta VA and Emory. The lab focuses on understanding the genetic basis of brain illnesses. They collaborated on the study with investigators at Emory’s Center of Neurodegenerative Disease.

In seeking new therapies, the research team, with support from VA and the National Institutes of Health, aimed to identify brain proteins that likely cause depression. The team hypothesized that genetic variants influence depression by altering levels of certain brain proteins.

Genome-wide association studies played a key role in the research but were not sufficient by themselves, explained Thomas Wingo. GWAS is an important tool for its ability to spot variations associated with medical conditions, including depression, but the genome scans do not shed light on how genetic variations translate into increased disease risk. So the study design combined GWAS and human brain proteomic data toward answering the question, how can variations in brain protein levels explain some of the inherited risk for depression?

By examining proteins—which are the final products of gene expression and the main functional components of cells—PWAS can help elucidate the biological mechanisms underlying depression. The approach can importantly supplement information from GWAS by finding changes in the way a protein is being expressed in a normal gene versus a variant. Despite proteins’ promise as biological informants, and in spite of the fact that proteins make up the bulk of drug targets and biomarkers, this study was conspicuous among depression studies for its direct look at proteins.

Biomarkers for depressive symptoms

It was this rare scientific method—using  the “largest and deepest reference human brain proteomes and summary statistics from the latest GWAS of depression,” according to the authors—that allowed the researchers to identify the total of 25 proteins of interest, 20 of which prior GWAS studies did not peg as implicated in depression.

As for the 19 genes they homed in on, the researchers determined they “contribute to depression pathogenesis through modulating their brain protein abundance.” The brain protein fluctuations detected by uniting GWAS and human brain proteomic data are likely among the earlier biological changes in depression and may predispose a person to the illness, said Aliza Wingo, making the findings particularly compelling in terms of therapeutic potential.

Follow-up research, including tests in model systems, is crucial to further examine the identified genes’ possible roles in depression and to seek additional implicated genes and proteins, the study authors said. The provocative suggestion that the implicated proteins appear to contribute to the inherited risk of depression has spurred ongoing work at the Wingos’ lab.

“We are very excited to continue to work on these promising targets in our lab but caution that the road leading to new drugs is long and difficult,” said Thomas Wingo, noting another clinical hope based on this area of study: “We take heart that these findings could also prove useful as biomarkers for depressive symptoms. An effective biomarker—like hemoglobin A1C for diabetes—could help with diagnosis and management of depression.”

Featured image: In their lab at the Atlanta VA and Emory University, Dr. Thomas Wingo and Dr. Aliza Wingo (foreground) have found genes and corresponding proteins that could open doors for new depression treatments. (This photo by Lisa Pessin was taken before the current pandemic.)

Reference: Thomas Wingo et al., “Brain proteome-wide association study implicates novel proteins in depression pathogenesis, Nature Neuroscience (2021). DOI: 10.1038/s41593-021-00832-6

Provided by US Department of Veteran Affairs

Pain Receptors Linked To The Generation Of Energy-burning Fat Cells (Biology)

Vascular smooth muscle-derived Trpv1+ progenitors have found to be a source of cold-induced “brown fat”

A new source of energy expending brown fat cells has been uncovered by researchers at the Joslin Diabetes Center, which they say points towards potential new therapeutic options for obesity. According to the new report, published in Nature Metabolism >on 12 March 2021, the key lies in the expression of a receptor called Trpv1 (temperature-sensitive ion channel transient receptor potential cation subfamily V member 1) — a protein known to sense noxious stimuli, including pain and temperature.

Specifically, the authors point to smooth muscle cells expressing the Trpv1 receptor and identify them as a novel source of energy-burning brown fat cells (adipocytes). This should translate into increased overall energy expenditure – and ultimately, researchers hope reduced weight.

Brown fat or brown adipose tissue is a distinct type of fat that is activated in response to cold temperatures. Its primary role is to produce heat to help maintain body temperature and it achieves that by burning calories. This has raised the prospect that such calorie burning can be translated into weight loss, particularly in the context of obesity.

“The capacity of brown and beige fat cells to burn fuel and produce heat, especially upon exposure to cold temperatures, have long made them an attractive target for treating obesity and other metabolic disorders,” said senior author Yu-Hua Tseng. “And yet, the precise origins of cold-induced brown adipocytes and mechanisms of action have remained a bit of a mystery.”

The source of these energy-burning fat cells was previously considered to be exclusively related to a population of cells that express the receptor Pdgfrα (platelet-derived growth factor receptor alpha). However, wider evidence suggests other sources may exist. Identifying these other sources would then open up potential new targets for therapy that would get around the somewhat uncomfortable use of cold temperatures to try to treat obesity.

The team initially investigated the general cellular makeup of brown adipose tissue from mice housed at different temperatures and lengths of time. Notably, they employed modern single-cell RNA sequencing approaches to try to identify all types of cells present. This avoided issues of potential bias towards one particular cell type – a weakness of previous studies, according to the authors.

“Single-cell sequencing coupled with advanced data analysis techniques has allowed us to make predictions in silico about the development of brown fat,” said co-author Matthew D. Lynes. “By validating these predictions, we hope to open up new cellular targets for metabolic research.”

As well as identifying the previously known Pdgfrα-source of energy-burning brown fat cells, their analysis of the single-cell RNA sequencing data suggested another distinct population of cells doing the same job – cells derived from smooth muscle expressing Trpv1*. The receptor has previously been identified in a range of cell types and is involved in pain and heat sensation.

Further investigations with mouse models confirmed that the Trpv1-positive smooth muscle cells gave rise to the brown energy-burning version of fat cells especially when exposed to cold temperatures. Additional experiments also showed that the Trpv1-positive cells were a source for beige fat cells that appear in response to cold in white fat, further expanding the potential influence of Trpv1-expressing precursor cells.

“These findings show the plasticity of vascular smooth muscle lineage and expand the repertoire of cellular sources that can be targeted to enhance brown fat function and promote metabolic health,” added the lead author.

Brown adipose tissue is the major thermogenic organ in the body and increasing brown fat thermogenesis and general energy expenditure is seen as one potential approach to treating obesity, added Shamsi.

“The identification of Trpv1-expressing cells as a new source of cold-induced brown or beige adipocytes suggests it might be possible to refine the use of cold temperatures to treat obesity by developing drugs that recapitulate the effects of cold exposure at the cellular level,” said Tseng.

The authors note that Trpv1 has a role in detecting multiple noxious stimuli, including capsaicin (the pungent component in chili peppers) and that previous studies suggest administration in both humans and animals results in reduced food intake and increased energy expenditure.

Tseng added: “Further studies are now planned to address the role of the Trpv1 channel and its ligands and whether it is possible to target these cells to increase numbers of thermogenic adipocytes as a therapeutic approach towards obesity.”

Other contributors to the research include Mary Piper (Harvard T.H. Chan School of Public Health, Boston, MA), Li-Lun Ho (Massachusetts Institute of Technology, Cambridge, MA), Tian Lian Huang (Joslin Diabetes Center), Anushka Gupta and Aaron Streets (University of California-Berkley, CA).

Funding for the study was provided by US National Institutes of Health grants, the National Institute of Diabetes and Digestive and Kidney Diseases and the American Diabetes Association. Full details are available in the Nature Metabolism report.

Featured image: Brown adipocytes derived from progenitors expressing the Trpv1 receptor are labeled with Green Fluorescent Protein (GFP) and are found in brown adipose tissue of mice exposed to cold temperature. ( © Joslin Diabetes Center 2021)

Reference: Shamsi et al. Vascular smooth muscle-derived TRPV1-positive progenitors are a new source of cold-induced thermogenic adipocytes. Nature Metabolism 2021, 3: XX-XX. Link to paper.

Provided by Joslin Diabetes Center

Early Cannabis Use Linked to Heart Disease, Say U of G Researchers (Medicine)

Using cannabis when you’re young may increase your risk of developing heart disease later, according to a recent University of Guelph study.

In the first study to look at specific risk indicators for cardiovascular disease (CVD) in young, healthy cannabis users, researchers found subtle but potentially important changes in heart and artery function.

Cigarette smoking is known to affect cardiovascular health, causing changes to blood vessels and the heart. Less is known about the impact of smoking cannabis on long-term CVD risk, even as use of the substance grows in Canada and abroad. Cannabis is the most commonly used recreational substance worldwide after alcohol.

“Cannabis is really widely used as a recreational substance all around the world and is becoming increasingly so,” said Christian Cheung, a PhD student in the Human Performance and Health Research Lab, part of the Department of Human Health and Nutritional Sciences (HHNS). “Scientists haven’t done that research with cannabis.”

Christian Cheung © University of Guelph

Cheung is the lead author of the study, published recently in the Journal of Applied Physiology. His co-authors were Dr. Jamie Burr and Dr. Philip Millar, both professors in HHNS and PhD student Alexandra Coates.

The team studied 35 subjects aged 19 to 30, half of whom were cannabis users. For all subjects, they used ultrasound imaging to look at the heart and arteries. They measured arterial stiffness and arterial function, or the ability of arteries to appropriately expand with greater blood flow. All three measures are indicators of cardiovascular function and potential disease risk.

Arterial stiffness was greater in cannabis users than in non-users. The team measured how fast a pressure wave travelled down the artery; stiffer arteries transmit a wave more quickly.

In cannabis users, cardiac function – inferred from how the heart moves as seen in echocardiographic images — was lower than in non-users.

Cheung said the team was surprised to see no difference in artery dilation in response to changing blood flow.

All three measures normally change in cigarette smokers, with stiffer arteries and lower vascular and heart function.

“We don’t yet know why in cannabis users there’s no difference in vascular function,” he said.

Cheung said differences may reflect variations in how tobacco and cannabis are consumed, as well as amounts and frequency and the user’s age.

“We looked at young cannabis users. In the cigarette literature, heavy, long-term smokers show reduced vascular function but that’s not necessarily the case for younger smokers.”

Dr. Jamie Burr © University of Guelph

The U of G researchers plan further studies to learn about potential impacts of these changes and disease risk in people who use cannabis.

“This is exciting new data, suggesting that even before more overt signs and symptoms of cardiovascular disease are present, there may be more subtle indications in altered physiological function,” said Burr.

“It also paves the way to our next studies, aimed at understanding the direct effects of cannabis consumption, and how this may interact with common stressors of everyday life, like exercise.”

Cheung emphasized that few studies have been done on the impacts of cannabis use on cardiovascular health.

“This is an exciting field of research given the ubiquity of cannabis use and the knowledge gap that exists, it’s a field ripe with opportunity.”

Featured image credit: Unsplash

Reference: Christian P. Cheung, Alexandra M. Coates, Philip J. Millar, and Jamie F. Burr, “Habitual cannabis use is associated with altered cardiac mechanics and arterial stiffness, but not endothelial function in young healthy smokers”, Journal of Applied Physiology 2021 130:3, 660-670. https://doi.org/10.1152/japplphysiol.00840.2020

Provided by University of Guelph

Breakthrough in Plant Protection: RNAi Pesticides Affect Only One Pest Species (Agriculture)

The detrimental impact of pesticides on non-target organisms is one of the most urgent concerns in current agriculture. Double-stranded RNAs (dsRNAs) represent the most species-specific class of pesticides to date, potentially allowing control of a target pest without effecting other species. The unprecedented target-specificity of dsRNA is due to its nucleotide sequence-specific mode of action that results in post-transcriptional gene silencing, or RNA interference (RNAi), in the target species. The development and field use of dsRNAs, via both the insertion of transgenes into the plant genome and the application of dsRNA sprays, is a rapidly growing area of research. Simultaneously, there exists the growing prospect of harnessing RNAi within integrated pest management schemes.

Using the pollen beetle (Brassicogethes aeneus) and its host crop oilseed rape (Brassica napus) as a model crop?pest system, a team of researchers collectively from Estonian University of Life Sciences, Ghent University and Maastricht University examined how RNAi efficacy depends on duration of dietary exposure to dsRNA. To this end, the authors applied dsRNA (specifically designed to induce RNAi in the pollen beetle) to oilseed rape flowers, and analyzed RNAi-induced mortality between insects chronically fed dsRNA and insects fed dsRNA for 3 days. Most notably, their data suggest that, with chronic dietary exposure to dsRNA, reduced dsRNA concentrations can be applied in order to achieve a similar effect compared to short-term (e.g. 3 days) exposure to higher concentrations. This observation has important implications for optimizing dsRNA spray approaches to managing crop pests. Specifically, while crop pest management is likely to benefit from successive dsRNA spray treatments, this may still be of economic benefit in practice because lower concentrations (e.g. 5?10 times lower) may be suitable for an equally effective outcome.

This work is timely, as dsRNA spray approaches are increasingly under consideration due to not only reduced biotechnology requirements, but also less legal restrictions in certain countries (e.g. member states of the European Union), compared to the engineering and cultivation of RNAi cultivars. The study adds new insights to the current discussion surrounding the potential benefits of genetically engineered crops. Transgenic RNAi cultivars continuously produce the species-specific dsRNA within the plant’s tissues, chronically exposing the target species to the pesticide as long as the pest continuously feeds on the crop. Thus, the authors highlight the need for research into the development and potential use of genetically engineered RNAi oilseed rape cultivars, given the enhanced RNAi efficacy resulting from chronic dsRNA feeding in the pollen beetle.

The work has been published, and is available online via Communications Biology (nature.com/commsbio) as of 6 April 2021.

The work was supported the Internalisation Programme DoRa (carried out by the Archimedes Foundation), institutional Research Funding projects IUT36-2 and PRG1056 of the Estonian Research Council, European ERA-NET C-IPM project “IPM4Meligethes” (project 3G0H0416), the European Union’s European Regional Development Fund (Estonian University of Life Sciences ASTRA project “Value-chain based bioeconomy”), the Special Research Fund (BOF) of Ghent University and the Research Foundation – Flanders (FWO-Vlaanderen).

Featured image: The harmfulness of pesticides to beneficial organisms is one of the most serious concerns in agriculture. Therefore scientists are eagerly looking for new, more environmentally friendly and species-specific solutions. Researchers at the Estonian University of Life Sciences, Ghent and the University of Maastricht took a long step forward in this regard. © Estonian University of Life Sciences

Reference: Willow J, Soonvald L, Sulg S, Kaasik R, Silva AI, Taning CNT, Christiaens O, Smagghe G, Veromann E (2021) RNAi efficacy is enhanced by chronic dsRNA feeding in pollen beetle. Communications Biology. DOI: 10.1038/s42003-021-01975-9

Provided by Estonian Research Council

Brain Damage Caused By Plasticisers: Bayreuth Biologists Investigate Effects of Bisphenols On Nerve Cells (Neuroscience)

The plasticisers contained in many everyday objects can impair important brain functions in humans. Biologists from the University of Bayreuth warn of this danger in an article in “Communications Biology”. Their study shows that even small amounts of the plasticisers bisphenol A and bisphenol S disrupt the transmission of signals between nerve cells in the brains of fish. The researchers consider it very likely that similar interference can also occur in the brains of adult humans. They therefore call for the rapid development of alternative plasticisers that do not pose a risk to the central nervous system. 

Bisphenols are plasticisers that are found in a large number of plastic products worldwide – for example, in food packaging, plastic tableware, drinking bottles, toys, tooth fillings, and babies’ dummies. In recent years, numerous health risks have already been associated with them, especially with bisphenol A (BPA). The Bayreuth research team led by Dr. Peter Machnik at the Animal Physiology research group (led by Prof. Dr. Stefan Schuster) has now for the first time investigated the effects of plasticisers on signal transmission between nerve cells in the adult brain. The study covers not only BPA, but also bisphenol S (BPS), which is often considered less harmful to health. Their findings: Both plasticisers impair communication between the nerve cells of the brain.

Permanent damage to the nervous system

The harmful effects on the brain mainly affect the delicate balance between different neuronal functions. While some brain cells transmit signals that trigger a state of excitation in downstream cells, other brain cells have the function of inhibiting downstream cells. However, the coordination of both excitation and inhibition is essential for an intact central nervous system. “It is well known that numerous disorders in the nervous system of vertebrates are triggered by the fact that excitatory signals and inhibitory signals are not or only inadequately coordinated. So, it is all the more alarming that the plasticisers BPA and BPS significantly impair precisely this coordination,” explains Dr. Peter Machnik, lead author of the study.

Goldfish in an Animal Physiology laboratory at the University of Bayreuth. Photo: Christian Wißler.

“We were surprised how many vital brain functions in fish are affected by the plasticisers used in numerous industries. This damage, as we were able to show, does not occur immediately. However, when the brain cells are exposed to small amounts of BPA or BPS for a month, the damage is unmistakable,” says Elisabeth Schirmer, a doctoral student from Bayreuth and first author of the study. It turns out that the plasticisers influence the action potential of brain cells. They alter the chemical and electrical transmission of signals through the synapses. In addition, they disrupt the circuits that are important for the perception and processing of acoustic and visual stimuli.

Studies on Mauthner cells in goldfish

The discovery of the damage caused by plasticisers came from detailed studies on live goldfish. The focus was on the two largest nerve cells in fish brain, the Mauthner cells. They integrate all sensory stimuli, all of which must be processed quickly and in a precisely coordinated manner when predators approach. In this case, the Mauthner cells trigger life-saving escape reactions. Due to this function, which is essential for survival, they have become particularly robust in the course of evolution. Mauthner cells are able to ward off damaging influences to a certain extent, or to compensate for damage afterwards. This makes it all the more significant that plasticisers are able to cause irreparable damage to these cells.

Microscopic image of the Mauthner cell of a goldfish (scale bar: 200 micrometres correspond to 0.2 millimetres). The cell was stained using neurobiotin/streptavidin-Cy3. Photo: Peter Machnik.

Transferability of the results to humans –

Demand for alternative plasticisers

“The findings obtained through studies on fish brains justify the assessment that BPA and BPS can also seriously damage the brains of adult humans. Against this background, it is essential that science and industry develop new plasticisers to replace these bisphenols, while being safe for human health,” says Dr. Peter Machnik. Prof. Dr. Stefan Schuster adds: “The efficiency of the research techniques we used in our study could, in addition, prove a valuable aid in the development of alternative plasticisers. They make it possible to quickly and inexpensively test how a substance under consideration affects brain cells.”

Research Funding:

The research was funded by the German Research Foundation (DFG) as part of a Reinhart Koselleck project.


Elisabeth Schirmer, Stefan Schuster, Peter Machnik: Bisphenols exert detrimental effects on neuronal signaling in mature vertebrate brains. Communications Biology (2021), DOI: https://doi.org/10.1038/s42003-021-01966-w

Featured image: Dr. Peter Machnik in one of the laboratories at Animal Physiology at the University of Bayreuth. In the background: Set-up for the electrophysiological study of nerve cells in the brains of fish. Photo: Christian Wißler.

Provided by University of Bayreuth

SMART Discovers the Science Behind Varying Performance of Different Coloured LEDs (Chemistry)

The findings pave the way for development of more efficient, next-gen LEDs covering the entire visible spectrum

● New multifaceted method can directly observe compositional fluctuations in indium gallium nitride, a semiconductor material used in LEDs

● Research found that compositional fluctuations are potentially linked to the origin of drop in efficiency of higher indium content LEDs

● The method can be adapted and applied in other materials science studies to investigate compositional fluctuations

Researchers from the Low Energy Electronic Systems (LEES) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, together with Massachusetts Institute of Technology (MIT) and National University of Singapore (NUS) have found a method to quantify the distribution of compositional fluctuations in the indium gallium nitride (InGaN) quantum wells (QWs) at different indium concentrations.

An array of multi-colored LEDs periodically arranged to give off visible light; a combination of InGaN based red, blue, and green LEDs is essential to cover lighting demands efficiently © MIT-SMART

InGaN light emitting diodes (LEDs) have revolutionised the field of solid-state lighting due to their high efficiencies and durability, and low costs. The colour of the LED emission can be changed by varying the indium concentration in the InGaN compound, giving InGaN LEDs the potential to cover the entire visible spectrum. InGaN LEDs with relatively low indium amounts compared to gallium, such as the blue, green, and cyan LEDs, have enjoyed significant commercial success for communication, industry and automotive applications. However, LEDs with higher indium concentrations, such as the red and amber LEDs, suffer from a drop in efficiency with the increasing amount of indium.

Currently, red and amber LEDs are made using the aluminium indium gallium phosphide (AlInGaP) material instead of InGaN due to InGaN’s poor performance in the red and amber spectrum caused by the efficiency drop. Understanding and overcoming the efficiency drop is the first step towards developing InGaN LEDs covering the whole visible spectrum that would significantly reduce production costs.

In a paper titled “Unlocking the origin of compositional fluctuations in InGaN light emitting diodes”, recently published in the prestigious journal Physical Review Materials, the team employed a multifaceted method to understand the origin of compositional fluctuations and their potential effect on the efficiency of InGaN LEDs. The accurate determination of compositional fluctuations is critical to understanding their role in reducing efficiency in InGaN LEDs with higher indium compositions.

“The [origin of the] efficiency drop experienced in higher indium concentration InGaN LEDs is still unknown to this date,” says co-author of the paper, Professor Silvija Gradecak from the Department of Materials Science and Engineering at NUS and Principal Investigator at SMART LEES. “It is important to understand this efficiency drop to create solutions that will be able to overcome it. In order to do so, we have designed a method that is able to detect and study the compositional fluctuations in the InGaN QWs to determine its role in the efficiency drop.”

The researchers developed a multifaceted method to detect indium compositional fluctuations in the InGaN QWs using synergistic investigation that combines complementary computational methods, advanced atomic-scale characterization and autonomous algorithms for image processing.

Tara Mishra, lead author of the paper and SMART PhD Fellow said, “This method developed and used in our research is of general applicability and can be adapted to other materials science investigations where compositional fluctuations need to be investigated.”

“The method that we developed can be widely applied and provide significant value and impact on other materials science studies, where atomistic compositional fluctuations play an important role in material performance,” said Dr Pieremanuele Canepa, co-author of the paper and Principal Investigator at SMART LEES and also Assistant Professor from the Department of Materials Science and Engineering, and Department of Chemical and Biomolecular Engineering at NUS. “The understanding of the atomic distribution of InGaN at varying indium concentrations is key to developing next-generation full-colour displays using the InGaN LED platform.”

The research found that the indium atoms are randomly distributed in a relatively low indium content InGaN. On the other hand, partial phase separation is observed in higher indium content InGaN, where random compositional fluctuations are concurrent with pockets of indium-rich regions.

The findings advanced the understanding of the atomic microstructure of the InGaN and its potential effect on the performance of LEDs, paving the way for future research to determine the role of compositional fluctuations in the new generation of InGaN LEDs and design strategies to prevent the degradation of these devices.

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) programme.

Reference: Tara P. Mishra, Govindo J. Syaranamual, Zeyu Deng (邓泽宇), Jing Yang Chung, Li Zhang, Sarah A. Goodman, Lewys Jones, Michel Bosman, Silvija Gradečak, Stephen J. Pennycook, and Pieremanuele Canepa, “Unlocking the origin of compositional fluctuations in InGaN light emitting diodes”, Phys. Rev. Materials 5, 024605 – Published 22 February 2021. https://journals.aps.org/prmaterials/abstract/10.1103/PhysRevMaterials.5.024605

Provided by SMART-MIT

Chemists at St. Petersburg University Create Renewable Plant-based Polymers (Material Science)

What makes them different is that they can be easily recycled

Researchers at the Laboratory of Cluster Catalysis at St Petersburg University have synthesised polymers from biomass. What makes them different is that they can be easily recycled.

Today, our life is simply unthinkable without polymers. Plastics, fibres, films, paint and lacquer coating – they are all polymers. We use them both in our everyday life and in industry. Yet the goods made from polymers, e.g. bottles, bags, or disposable tableware, are used just once or for a short period of time before they are thrown away. Due to the chemical compounds that they may release during recycling, they pose a real threat to our environment.

There are few polymers that can be recycled many times. This stirs up interest in secondary recycling. However, the goods made from secondary raw materials are lower in quality compared to the goods from primary raw materials.

The new polymers are based on biomass compounds. Biomass is a renewable source of raw materials for the chemical industry of the future. The key component of these polymers is terpenols, i.e. compounds from natural alcohols. Among them are such well-known examples as: menthol derived from the essential oil in mint; and borneol – a large quantity of which can be found in the essential oil in the white fir tree.

The synthesised polymers may well be used for primary and secondary recycling. During secondary recycling, the polymer-based products can be converted into the primary compounds. This may be further followed by polymerisation. These polymers can be recycled at moderate temperatures.

‘This can be said about recycling the materials based on our polymers. If they are recycled without oxygen, we can get natural alcohols or their derivatives that can be restored to the same alcohols. Because they are widely found in nature, they do not harm the environment,’ said Svetlana Metlyaeva, the first author of the article and a researcher at the Laboratory of Cluster Catalysis at St Petersburg University.

The polymers of this type can be melted at about 120°C and shaped in another way, she said. When cooling, they become hard. Interestingly, the chemists repeated this cycle seven times and concluded that the polymers, when melted more than once, did not change their properties.

The researchers are planning to continue their work at the Research Park at St Petersburg University. They will study the mechanical properties of the polymers, including resilience, elasticity, strength, and others. This is an important step towards our understating of how to use them in industry.

‘What we have achieved so far is only the ability to synthesise these polymers. Yet the properties of the polymer-based materials can vary. This depends on the way in which we synthesise them and what compounds we use. Now we have to modify the polymers themselves and the materials based on them. Then we will be able to talk about how we can use them,’ said Svetlana Metlyaeva.

Featured image: Mechanical treatment of mitranol-based polymers: ? – primary polymer as white powder; b – melted polymer, c-f – various forms of the polymer after being melted repeatedly © SPbU

Reference: Svetlana A. Metlyaeva et al., “Biomass- and calcium carbide-based recyclable polymers”, Green Chemistry, 2021. https://pubs.rsc.org/en/content/articlelanding/2021/gc/d0gc04170j#!divAbstract

Provided by St. Petersburg State University