Neuroscience

Researchers at King’s College London have discovered how a molecular ‘scaffold’ which allows key parts of cells to interact, comes apart in dementia and motor neuron disease, revealing a potential new target for drug discovery.

The study, published today in Nature Communications, was funded by the UK Medical Research Council, Wellcome Trust, Alzheimer’s Research UK and the Motor Neurone Disease Association.

Researchers looked at two components of cells: mitochondria, the cell ‘power houses’ which produce energy for the cell;and the endoplasmic reticulum (ER) which makes proteins and stores calcium for signalling processes in the cell. ER and mitochondria form close associations and these interactions enable a number of important cell functions. However the mechanism by which ER and mitochondria become linked has not, until now, been fully understood.

Professor Chris Miller, from the Department of Neuroscience at the Institute of Psychiatry at King’s and lead author of the paper, says: “At the molecular level, many processes go wrong in dementia and motor neuron disease,and one of the puzzles we’re faced with is whether there is a common pathway connecting these different processes. Our study suggests that the loosening of this ‘scaffold’ between the mitochondria and ER in the cell may be a key process in neurodegenerative diseases such as dementia or motor neuron disease.”

By studying cells in a dish, the researchers discovered that an ER protein called VAPB binds to a mitochondrial protein called PTPIP51, to form a ‘scaffold’ enabling ER and mitochondria to form close associations. In fact, by increasing the levels of VAPB and PTPIP51, mitochondria and ER re-organised themselves to form tighter bonds.

Many of the cell’s functions that are controlled by ER-mitochondria associations are disrupted in neurodegenerative diseases, so the researchers studied how the strength of this ‘scaffold’ was affected in these diseases. TDP-43 is a protein which is strongly linked to Amyotrophic Lateral Sclerosis (ALS, a form of motor neuron disease) and Fronto-Temporal Dementia (FTD, the second most common form of dementia), but exactly how the protein causes neurodegeneration is not properly understood.

The researchers studied how TDP-43 affected mouse cells in a dish. They found that higher levels of TDP-43 resulted in a loosening of the scaffold which reduced ER-mitochondria bonds,affecting some important cellular functions that are linked to ALS and FTD.

Professor Miller concludes: “Our findings are important in terms of advancing our understanding of basic biology, but may also provide a potential new target for developing new treatments for these devastating disorders.”

Deep sleep promotes our well-being, improves our memory and strengthens the body’s defences. Zurich and Fribourg researchers demonstrate how restorative SWS can also be increased without medication – using hypnosis.

Sleeping well is a crucial factor contributing to our physical and mental restoration. SWS in particular has a positive impact for instance on memory and the functioning of the immune system. During periods of SWS, growth hormones are secreted, cell repair is promoted and the defence system is stimulated. If you feel sick or have had a hard working day, you often simply want to get some good, deep sleep. A wish that you can’t influence through your own will –  so the widely held preconception.  

Sleep researchers from the Universities of Zurich and Fribourg now prove the opposite. In a study that has now been published in the scientific journal “Sleep”, they have demonstrated that hypnosis has a positive impact on the quality of sleep, to a surprising  extent. “It opens up new, promising opportunities for improving the quality of sleep without drugs”, says biopsychologist Björn Rasch who heads the study at the Psychological Institute of the University of Zurich in conjunction with the “Sleep and Learning” project*.

Brain waves ­– an indicator of sleep quality

Hypnosis is a method that can influence processes which are very difficult to control voluntarily. Patients with sleep disturbances can indeed be successfully treated with hypnotherapy. However, up to now it hadn’t been proven that this can lead to an objectively measurable change in sleep. To objectively measure sleep, electrical brain activity is recorded using an electroencephalogram (EEG). The characteristic feature of slow-wave sleep, which is deemed to have high restorative capacity, is a very even and slow  oscillation in electrical brain activity.

70 healthy young women took part in the UZH study. They came to the sleep laboratory for a 90-minute midday nap. Before falling asleep they listened to a special 13-minute slow-wave sleep hypnosis tape over loudspeakers, developed by hypnotherapist Professor Angelika Schlarb, a sleep specialist, or to a neutral spoken text. At the beginning of the experiment the subjects were divided into highly suggestible and low suggestible groups using a standard procedure (Harvard Group Scale of Hypnotic Susceptibility). Around half of the population is moderately suggestible. With this method women achieve on average higher values for hypnotic susceptibility than men. Nevertheless, the researchers expect the same positive effects on sleep for highly suggestible men.

Slow-wave sleep increased by 80 percent

In their study, sleep researchers Maren Cordi and Björn Rasch were able to prove that highly suggestible women experienced 80 percent more slow-wave sleep after listening to the hypnosis tape compared with sleep after listening to the neutral text. In parallel, time spent awake was reduced by around one-third. In contrast to highly suggestible women, low suggestible female participants did not benefit as much from hypnosis. With additional control experiments the psychologists confirmed that the beneficial impact of hypnosis on slow-wave sleep could be attributed to the hypnotic suggestion to “sleep deeper” and could not be reduced to mere expectancy effects.

According to psychologist Maren Cordi “the results may be of major importance for patients with sleep problems and for older adults. In contrast to many sleep-inducing drugs, hypnosis has no adverse side effects”. Basically, everyone who responds to hypnosis could benefit from improved sleep through hypnosis.  

* The project “Sleep and Learning” is headed by Professor Björn Rasch from the University of Fribourg and conducted at the Universities of Zurich and Fribourg. The project is financed by the Swiss National Fund and the University of Zurich (main area of clinical research “Sleep and Health”). The goal of the project is to identify psychological and neurophysiological mechanisms underlying the positive role of sleep for our memory and mental health.  

Fetuses are more likely to show left-handed movements in the womb when their mothers are stressed, according to new research.

Researchers at Durham and Lancaster universities say their findings are an indicator that maternal stress could have a temporary effect on unborn babies, adding that their research highlights the importance of reducing stress during pregnancy.

However, the researchers emphasised that their study was not evidence that maternal stress led to fixed left-handedness in infants after birth. They said that some people might be genetically predisposed to being left-handed and that there are examples where right and left-handedness can switch throughout a person’s life.

Using 4d ultrasound scans, the researchers observed 57 scans of 15 healthy fetuses, recording 342 facial touches.

The fetuses were scanned at four different stages between 24 and 36 weeks of pregnancy. Researchers also asked the mothers of these babies how much stress they had experienced in the four weeks between each of the scans.

The researchers found that the more stress mothers reported, the more frequently fetuses touched their faces with their left hands. They added that a significant number of touches by the fetuses of stressed mothers were done with their left, rather than right hands - therefore fetal touches of their own faces, indicated a left-handed tendency.

As right-handedness is more common in the general population, the researchers had expected to see more of a bias towards right-handed movements in the fetuses as they grew older. The high percentage of left-handed behaviour, observed only when mothers reported being stressed, led them to conclude that maternal stress has an effect on the lateral behaviour of the babies they scanned.

The findings are published in the journal Laterality: Asymmetries of Body, Brain and Cognition.

Lead author Dr Nadja Reissland, in Durham University’s Department of Psychology, said: “Our research suggests that stressed mothers have fetuses who touch their face relatively more with their left hand.

“This suggests maternal stress could be having on effect on the child’s behaviour in the womb and highlights the importance of reducing maternal stress in pregnancy.

“Such measures may include increased emphasis on stopping stressful work early, the inclusion of relaxation classes in pre-natal care and involvement of the whole family in the pre-natal period.

“While we observed a higher degree of left-handed behaviour in the fetuses of stressed mothers than had been expected, we are not saying that maternal stress leads to a child becoming left-handed after birth, as there could be a number of reasons for this.

“The research does suggest, however, that a fetus can detect when a mother is stressed and that it responds to this stress.”

Professor Brian Francis, of Lancaster University, emphasised that the study also showed that overall preference for left or right hand varied considerably from scan to scan within each fetus, though fetuses showed more left-hand movements when mothers reported that they had experienced stress. He said: “Overall, there was no consistent handedness preference being shown by the fetuses, with most fetuses switching in preference at least once over the four scans.”

The researchers added that while mothers were asked to report their stress levels in the four weeks between scans, in practice some might have reported the stress they were experiencing at the time of being surveyed.

Previous research has shown that maternal stress in pregnancy leads to increased levels of cortisol – a hormone produced in response to stress - in mothers that could lead to an altered preference for left-sided or right-sided behaviour in fetuses.

The current study did not assess the stress levels of fetuses and Dr Reissland said that future research could examine cortisol levels in fetuses to further determine the effect of stress on lateral behaviour.

Dr Reissland added that further research was also needed to look at whether or not maternal prenatal stress had longer-term effects on the development of infants and children after birth.

A seven-year study of women who take antipsychotic medication while pregnant, proves it can affect babies.

The observational study, published in the journal PLOS ONE, reveals that whilst most women gave birth to healthy babies, the use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the need for special care after birth with 43 per cent of babies placed in a Special Care Nursery (SCN) or a Neonatal Intensive Care Unit (NICU), almost three times the national rate in Australia.

As well as an increased likelihood of the need for intensive care, the world-first study by experts from the Monash Alfred Psychiatry Research Centre (MAPrc) and Monash University, shows antipsychotic drugs affects babies in other ways; 18 per cent were born prematurely, 37 per cent showed signs of respiratory distress and 15 per cent developed withdrawal symptoms.

Principal investigator, Professor Jayashri Kulkarni, Director of MAPrc, said the study highlights the need for clearer health guidelines when antipsychotic drugs are taken during pregnancy.

“There’s been little research on antipsychotic medication during pregnancy and if it affects babies. The lack of data has made it very difficult for clinicians to say anything conclusively on how safe it is for babies,” Professor Kulkarni said.

“This new research confirms that most babies are born healthy, but many experience neonatal problems such as respiratory distress.”

With no existing data to draw on, MAPrc established the world-first National Register of Antipsychotic Medications in Pregnancy (NRAMP) in 2005. Women who were pregnant and taking antipsychotic medication were recruited from around Australia through clinical networks in each state and territory. In all 147 women were interviewed every six weeks during pregnancy and then followed until their babies were one year old.

Antipsychotic drugs are currently used to treat a range of psychiatric disorders including schizophrenia, major depression and bipolar disorder. About 20 per cent of Australian women experience depression in their lifetime, compared to 10 per cent of men. In Australia 25 per cent of women experience postnatal depression and 20 per cent experience severe menopausal depression.

Women have much higher rates of anxiety disorders and there are equal percentages of men and women with schizophrenia (2 per cent) and bipolar disorder (about 3 per cent).

Professor Kulkarni said the emergence of new antipsychotic drugs means that many women with a well controlled psychiatric disorder are able to contemplate having babies, but there have always been concerns about the effect of treatment on their offspring.

“The potentially harmful effects of taking an antipsychotic drug in pregnancy have to be balanced against the harm of untreated psychotic illness. The good news is we now know there are no clear associations with specific congenital abnormalities and these drugs,” Professor Kulkarni said.

“However clinicians should be particularly mindful of neonatal problems such as respiratory distress, so it’s critical that Neonatal Intensive Care Units, or Special Care Nurseries are available for these babies.”

A team of University of South Carolina researchers led by Mitzi Nagarkatti, Prakash Nagarkatti and Xiaoming Yang have discovered a novel pathway through which marijuana can suppress the body’s immune functions. Their research has been published online in the Journal of Biological Chemistry.

Marijuana is the most frequently used illicit drug in the United States, but as more states legalize the drug for medical and even recreational purposes, research studies like this one are discovering new and innovative potential health applications for the federal Schedule I drug.

Marijuana is now regularly and successfully used to alleviate the nausea and vomiting many cancer patients experience as side effects to chemotherapy, combat the wasting syndrome that causes some AIDS patients to lose significant amounts of weight and muscle mass and ease chronic pain that is unresponsive to opioids, among other applications.

The university study has uncovered yet another potential application for marijuana, in the suppression of immune response to treat autoimmune diseases. The work builds on recent scientific discoveries that the environment in which humans live can actually trigger changes that occur outside of human DNA, but nevertheless can cause alterations to the function of genes controlled by DNA. These outside molecules that have the ability to alter DNA function are known collectively as the epigenome. In this study, the investigators wanted to find out if the tetrahydrocannabinol found in marijuana has the capacity to affect DNA expression through epigenetic pathways outside of the DNA itself.

The recent findings show that marijuana THC can change critical molecules of epigenome called histones, leading to suppression of inflammation. These results suggest that one potential negative impact of marijuana smoking could be suppression of beneficial inflammation in the body. But they also suggest that, because of its epigenetic influence toward inflammation suppression, marijuana use could be efficacious in the treatment of autoimmune diseases such as arthritis, lupus, colitis, multiple sclerosis and the like, in which chronic inflammation plays a central role.

Until now, scientists have not known exactly how inflammation weakens the Blood-Brain Barrier, allowing toxins and other molecules access to the brain. A new research report appearing in the June 2014 issue of The FASEB Journal solves this mystery by showing that a molecule, called “microRNA-155,” is responsible for cleaving epithelial cells to create microscopic gaps that let material through. Not only does this discovery help explain the molecular underpinnings of diseases like multiple sclerosis, but it also opens an entirely new avenue for developing therapies that can help penetrate the Blood-Brain Barrier to deliver lifesaving drugs.

According to Ignacio A, Romero, Ph.D., “We are beginning to understand the mechanisms by which the barrier between the blood and the brain becomes leaky in inflammatory conditions. Based on these and other findings, drugs that reduce the leakiness of the barrier have the potential to improve symptoms in many neurological conditions.” Romero is one of the researchers involved in the work from the Department of Life, Health and Chemical Sciences of the Biomedical Research Network at The Open University in the United Kingdom.

To make this discovery, Romero and colleagues first measured microRNA-155 (miR-155) levels in cultured human cells and compared them to cells under inflammatory conditions. Researchers then measured levels in the blood vessels of inflamed brain areas of patients with multiple sclerosis (MS) and compared them to non-inflamed areas. In both cases, miR-155 was elevated in inflammation. Then, in mice, normal mice were compared with mice that were genetically altered to lose miR-155. When an inflammatory reaction was induced in these two groups of mice, the mice that could not express miR-155 had a much reduced increase in “leakiness” of the Blood-Brain Barrier than normal mice. Finally, scientists investigated in cultured human cells the mechanism by which miR-155 levels cause leakiness of the barrier and concluded that miR-155 affects the organization of the complex structures that form the tight connections between endothelial cells.

"This study has the potential to be a game-changer in terms of how we treat neurological conditions and how we deliver drugs to the brain," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Since it was first discovered, the Blood-Brain Barrier has always been a touch elusive. Now, after careful analysis, we are learning exactly how our bodies keep our brains safe and that microRNA-155 is a key player.”

Twenty years after the hormone leptin was found to regulate metabolism, appetite, and weight through brain cells called neurons, Yale School of Medicine researchers have found that the hormone also acts on other types of cells to control appetite.

Published in the June 1 issue of Nature Neuroscience, the findings could lead to development of treatments for metabolic disorders such as obesity and diabetes.

"Up until now, the scientific community thought that leptin acts exclusively in neurons to modulate behavior and body weight," said senior author Tamas Horvath, the Jean and David W. Wallace Professor of Biomedical Research and chair of comparative medicine at Yale School of Medicine. "This work is now changing that paradigm."

Leptin, a naturally occurring hormone, is known for its hunger-blocking effect on the hypothalamus, a region in the brain. Food intake is influenced by signals that travel from the body to the brain. Leptin is one of the molecules that signal the brain to modulate food intake. It is produced in fat cells and informs the brain of the metabolic state. If animals are missing leptin, or the leptin receptor, they eat too much and become severely obese.

Leptin’s effect on metabolism has been found to control the brain’s neuronal circuits, but no previous studies have definitively found that leptin could control the behavior of cells other than neurons.

To test the theory, Horvath and his team selectively knocked out leptin receptors in the adult non-neuronal glial cells of mice. The team then recorded the water and food intake, as well as physical activity every five days. They found that animals responded less to feeding reducing effects of leptin but had heightened feeding responses to the hunger hormone ghrelin.

"Glial cells provide the main barrier between the periphery and the brain," said Horvath. "Thus glial cells could be targeted for drugs that treat metabolic disorders, including obesity and diabetes."

New research reveals that bilingualism has a positive effect on cognition later in life. Findings published in Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, show that individuals who speak two or more languages, even those who acquired the second language in adulthood, may slow down cognitive decline from aging.

Bilingualism is thought to improve cognition and delay dementia in older adults. While prior research has investigated the impact of learning more than one language, ruling out “reverse causality” has proven difficult. The crucial question is whether people improve their cognitive functions through learning new languages or whether those with better baseline cognitive functions are more likely to become bilingual.

"Our study is the first to examine whether learning a second language impacts cognitive performance later in life while controlling for childhood intelligence," says lead author Dr. Thomas Bak from the Centre for Cognitive Aging and Cognitive Epidemiology at the University of Edinburgh.

For the current study, researchers relied on data from the Lothian Birth Cohort 1936, comprised of 835 native speakers of English who were born and living in the area of Edinburgh, Scotland. The participants were given an intelligence test in 1947 at age 11 years and retested in their early 70s, between 2008 and 2010. Two hundred and sixty two participants reported to be able to communicate in at least one language other than English. Of those, 195 learned the second language before age 18, 65 thereafter.

Findings indicate that those who spoke two or more languages had significantly better cognitive abilities compared to what would be expected from their baseline. The strongest effects were seen in general intelligence and reading. The effects were present in those who acquired their second language early as well as late.

The Lothian Birth Cohort 1936 forms the Disconnected Mind project at the University of Edinburgh, funded by Age UK. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1) and has been made possible thanks to funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC).

"The Lothian Birth Cohort offers a unique opportunity to study the interaction between bilingualism and cognitive aging, taking into account the cognitive abilities predating the acquisition of a second language" concludes Dr. Bak. "These findings are of considerable practical relevance. Millions of people around the world acquire their second language later in life. Our study shows that bilingualism, even when acquired in adulthood, may benefit the aging brain."

After reviewing the study, Dr. Alvaro Pascual-Leone, an Associate Editor for Annals of Neurology and Professor of Medicine at Harvard Medical School in Boston, Mass. said, “The epidemiological study by Dr. Bak and colleagues provides an important first step in understanding the impact of learning a second language and the aging brain. This research paves the way for future causal studies of bilingualism and cognitive decline prevention.”

A collaborative effort between Duke Medicine researchers and neurosurgeons and scientists in China has produced new genetic insights into a rare and deadly form of childhood and young adult brain cancer called brainstem glioma.

The researchers identified a genetic mutation in the tumor cells that plays a role in both the growth and the death of a cell. Additionally, the mutation to the newly identified gene may also contribute to the tumor’s resistance to radiation.

The findings, published online in the journal Nature Genetics on June 1, 2014, provide both immediate and long-term benefits. Knowing that this mutation may render radiation ineffective, patients could be spared that therapy. The mutation would also serve as a strong candidate for drug development.

The researchers conducted genetic tests and found that many of the tumor cells had a mutation in a gene called PPM1D, which causes cells to proliferate and avoid natural death. It is the first time this mutation has been found to be a major driving force in the development of brainstem gliomas; it is not evident in other brain tumors.

If tumors have this PPM1D mutation, they do not have another more common genetic mutation to the TP53 gene, a tumor suppressor that, when defective, is linked to half of all cancers.

“This finding has immediate clinical applications, because either mutation - PPM1D or TP53 – cause the tumor cells to be resistant to radiation,” said senior author Hai Yan, M.D., Ph.D., a professor of pathology at Duke University School of Medicine. “Knowing that could spare patients from an ineffective treatment approach.”

Additionally, the PPM1D genetic mutation is a strong candidate for new drug development.

“This finding gives us a clue as to why these particular tumors are growing inappropriately,” said co-author Zachary Reitman, M.D., Ph.D., a research associate at Duke. “These clues may help us to design better treatments for this type of cancer.”

Yan said his lab is working to identify new treatments that could target the PPM1D genetic mutation and shut down its cancer-growing capabilities.

“PPM1D is itself a target for drug development, because the gene mutation causes cells to avoid death and proliferate,” Yan said. “In drug development, it’s easier to turn that growth function off than it is to switch on the cell’s defective tumor suppression mechanism.”

Research by scientists at Albert Einstein College of Medicine of Yeshiva University may help explain how some cases of autism spectrum disorder (ASD) can result from environmental influences rather than gene mutations. The findings, published online today in PLOS Genetics, shed light on why older mothers are at increased risk for having children with ASD and could pave the way for more research into the role of environment on ASD.

The U.S. Centers for Disease Control and Prevention announced in March that one in 68 U.S. children has an ASD—a 30 percent rise from 1 in 88 two years ago. A significant number of people with an ASD have gene mutations that are responsible for their condition. But a number of studies—particularly those involving identical twins, in which one twin has ASD and the other does not—show that not all ASD cases arise from mutations.

In fact, a major study of more than 14,000 children with ASDs published earlier this month in the Journal of the American Medical Association concluded that gene abnormalities could explain only half the risk for developing ASD. The other half of the risk was attributable to “nongenetic influences,” meaning environmental factors that could include the conditions in the womb or a pregnant woman’s stress level or diet. 

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Symmetry is an inherent part of development. As an embryo, an organism’s brain and spinal cord, like the rest of its body, organize themselves into left and right halves as they grow. But a certain set of nerve cells do something unusual: they cross from one side to the other. New research in mice delves into the details of the molecular interactions that help guide these neurons toward this anatomical boundary.

In an embryo, a neuron’s branches, or axons, have special structures on their tips that sense chemical cues telling them where to grow. The new findings, by researchers at Memorial Sloan Kettering Cancer Center and The Rockefeller University, reveal the structural details of how one such cue, Netrin-1, interacts with two sensing molecules on the axons, DCC and a previously less well characterized player known as neogenin, as a part of this process.

“Our work provides the first high-resolution view of the molecular complexes that form on the surface of a developing axon and tell it to move in one direction or another,” says Dimitar Nikolov, a structural biologist at Memorial Sloan Kettering. “This detailed understanding of these assemblies helps us better understand neural wiring, and may one day be useful in the development of drugs to treat spinal cord or brain injuries.”

In a developing nervous system, the signaling molecule, Netrin-1, identified by Rockefeller University Professor Marc Tessier-Lavigne and colleagues, can guide neurons by attracting or repulsing them. In the case of axons that cross from one side to the other, extended by so-called commissural neurons, Netrin-1 attracts them toward the middle.

With a technique that uses X-rays to visualize the structure of crystalized proteins, research scientist Kai Xu and colleagues in Nikolov’s laboratory revealed that Netrin-1 has two separate binding sites on opposite ends, enabling it to simultaneously bind to different receptors. This may explain how Netrin-1, which is an important axon-guiding molecule, can affect in different ways neurons that express different combinations of receptors, Nikolov says.

For some time, scientists have known commissural neurons used the receptor molecule DCC to detect Netrin-1. Neogenin has a structure similar to DCC, and this research, described today in Science, confirms neogenin too acts as a sensing molecule for commissural neurons in mammals.

In experiments that complemented the structural work, conducted by Nicolas Renier and Zhuhao Wu in Tessier-Lavigne’s lab, the researchers confirmed that, like DCC, neogenin senses Netrin-1 for the growing commissural neurons in mice.

These neurons are part of the system by which one side of the brain controls movement on the opposite side of the body. As a result, a mutation in the gene responsible for DCC interferes with this coordination, causing congenital mirror movement disorder. People with this disorder cannot move one side of the body in isolation; for example, a right-handed wave is mirrored by a similar gesture by the left hand.

The work also has implications for understanding why DCC, neogenin and other cell-surface receptors come in slightly different forms, called splice isoforms. The structural research revealed these isoforms bind differently to Netrin-1. However, it is not yet clear what this means for neuron wiring, Nikolov says.

“With this structural knowledge, and with the identification of an additional receptor involved in axon guidance in the spinal cord, we are gaining deeper insight into the mechanisms through which neurons make connections that produce a functioning nervous system, as well as the dysfunction that arises from miswiring of connections” says Tessier-Lavigne.

New research from the Monell Chemical Senses Center reveals that women’s faces are rated as more attractive in the presence of pleasant odors. In contrast, odor pleasantness had less effect on the evaluation of age. The findings suggest that the use of scented products such as perfumes may, to some extent, alter how people perceive one another.

“Odor pleasantness and facial attractiveness integrate into one joint emotional evaluation,” said lead author Janina Seubert, PhD, a cognitive neuroscientist who was a postdoctoral fellow at Monell at the time the research was conducted. “This may indicate a common site of neural processing in the brain.”

Perfumes and scented products have been used for centuries as a way to enhance overall personal appearance. Previous studies had shown perception of facial attractiveness could be influenced when using unpleasant vs. pleasant odors. However, it was not known whether odors influence the actual visual perception of facial features or alternatively, how faces are emotionally evaluated by the brain.

The current study design centered on the principle that judging attractiveness and age involve two distinct perceptual processing methods: attractiveness is regarded as an emotional process while judgments of age are believed to be cognitive, or rationally-based.

In the study, published in open access journal PLOS ONE, 18 young adults, two thirds of whom were female, were asked to rate the attractiveness and age of eight female faces, presented as photographs. The images varied in terms of natural aging features.

While evaluating the images, one of five odors was simultaneously released. These were a blend of fish oil (unpleasant) and rose oil (pleasant) that ranged from predominantly fish oil to predominantly rose oil. The subjects were asked to rate the age of the face in the photograph, the attractiveness of the face and the pleasantness of the odor.

Across the range of odors, odor pleasantness directly influenced ratings of facial attractiveness. This suggests that olfactory and visual cues independently influence judgments of facial attractiveness.

With regard to the cognitive task of age evaluation, visual age cues (more wrinkles and blemishes) were linked to older age perception. However, odor pleasantness had a mixed effect. Visual age cues strongly influenced age perception during pleasant odor stimulation, making older faces look older and younger faces look younger. This effect was weakened in the presence of unpleasant odors, so that younger and older faces were perceived to be more similar in age.

Jean-Marc Dessirier, Lead Scientist at Unilever and a co-author on the study said, “These findings have fascinating implications in terms of how pleasant smells may help enhance natural appearance within social settings. The next step will be to see if the findings extend to evaluation of male facial attractiveness.”

A new treatment for drug-resistant epilepsy with the potential to suppress seizures ‘on demand’ with a pill, similar to how you might take painkillers when you feel a headache coming on, has been developed by UCL researchers funded by the Wellcome Trust.

The treatment, described in Nature Communications, combines genetic and chemical approaches to suppress seizures without disrupting normal brain function. The technique was demonstrated in rodents but in future we could see people controlling seizures on-demand with a simple pill.

Epilepsy affects around 50 million people worldwide including 600,000 in the UK and around a quarter of cases are resistant to conventional treatments. Many of these cases could be addressed by the new treatment method, which relies on genetic modification of brain cells to make them sensitive to a normally inactive compound.

“First, we inject a modified virus into the area of the brain where seizures arise,” explains Professor Dimitri Kullmann of the UCL Institute of Neurology, senior author of the research. “This virus instructs the brain cells to make a protein that is activated by CNO (clozapine-N-oxide), a compound that can be taken as a pill. The activated protein then suppresses the over-excitable brain cells that trigger seizures, but only in the presence of CNO.

“At the moment, severe seizures are treated with drugs that suppress the excitability of all brain cells, and patients therefore experience side effects. Sometimes the dose required to stop seizures is so high that patients need to be sedated and taken to intensive care. If we can take our new method into the clinic, which we hope to do within the next decade, we could treat patients who are susceptible to severe seizures with a one-off injection of the modified virus, and then use CNO only when needed.

“CNO would be given as a pill in the event that patients could predict when seizures were likely to occur. For example, many people with treatment-resistant epilepsy experience clusters of seizures, where severe seizures are preceded by smaller ones. Seizure risk is also high when people are ill, sleep deprived, or at certain times of the menstrual cycle, so these would all be good times to take the pill as a preventative measure. In urgent situations, the compound could be given as an injection. We could even consider a fully automatic delivery system, where CNO was given by a pump, as is done for insulin in some people with diabetes.”

As CNO has a half-life of about a few hours and only affects the pre-treated epileptic parts of the brain, the new method avoids the need to permanently alter the brain or treat the whole brain with seizure-suppressing drugs. It builds on similar work by Professor Kullmann’s group using gene therapy to ‘calm down’ brain cells, or using light pulses to activate seizure-suppressing receptors in the brain. The new technique works in a similar way but is reversible and avoids the need for invasive devices to deliver light to the brain.

“After the one-off injection into affected areas of the brain, our new technique would require nothing beyond CNO, administered as an injection or a pill, to suppress seizures when required,” says Professor Kullmann. “This makes it more attractive than alternative forms of targeted therapy such as surgery to remove the brain region where seizures arise, or gene therapy that permanently alters the excitability of brain cells.

“Although there is currently no evidence that permanently suppressing excitability in a small area affects brain function, we cannot be sure that it would have no impact long-term. Our new method is completely reversible, so if there were any side-effects then people could simply stop taking the CNO pill.”

Virginia Commonwealth University School of Medicine researchers have uncovered a new mechanism of action of fingolimod, a drug widely used to treat multiple sclerosis: elimination of adverse or traumatic memories.

The findings shed light on how the drug works on the molecular level – something that has not been well understood until now.

Fingolimod, or FTY720, which is the first orally available drug for treatment of multiple sclerosis, works by suppressing the immune system. Fingolimod is a prodrug that is phosphorylated in the body to its active form, FTY720-phosphate.

In a study published by the Nature Neuroscience journal on May 25 as an Advanced Online Publication, researchers used a mouse model to show that fingolimod accumulates in the brain and inhibits histone deacetylases, which are enzymes important to regulate gene expression. The team observed an increased expression of a limited number of genes important for certain memory processes. Fingolimod acted similarly to the natural signaling lipid, sphingosine-1-phosphate, which it closely resembles.

“Our work suggests that some of the beneficial effects of FTY720/fingolimod that are not well understood might be mediated by this new activity that we have discovered,” said first author Sarah Spiegel, Ph.D., an internationally renowned researcher and professor and chair of the Department of Biochemistry and Molecular Biology in the VCU School of Medicine.

“It will be important in the future to determine whether this prodrug can reduce loss of cognitive functions and can erase adverse memories,” she said.

Spiegel added that other histone deacetylase inhibitors have long been used for treatment of psychiatric and neurological disorders, yet the mechanism of their effectiveness is not fully understood.

“FTY720/fingolimod may be a useful adjuvant therapy to help stop aversive memories such as in post-traumatic stress disorder and other anxiety disorders,” Spiegel said.

“The work has not been extended to show effectiveness in humans at this time. We are still working to fully understand the molecular underpinnings of the drug and its link to memory,” she said.

The work is based on previous findings by Spiegel’s group that were published in Science in 2009. They had reported that sphingosine-1-phosphate formed in the nucleus of cells is a natural inhibitor of histone deacetylases and a regulator of gene expression.

Puberty is the defining process of adolescent development, beginning a cascade of changes throughout the body, including the brain. Penn Medicine researchers have discovered that cerebral blood flow (CBF) levels decreased similarly in males and females before puberty, but saw them diverge sharply in puberty, with levels increasing in females while decreasing further in males, which could give hints as to developing differences in behavior in men and women and sex-specific pre-dispositions to certain psychiatric disorders. Their findings are available in Proceedings of the National Academy of Science (PNAS).

"These findings help us understand normal neurodevelopment and could be a step towards creating normal ‘growth charts’ for brain development in kids. These results also show what every parent knows: boys and girls grow differently. This applies to the brain as well," says Theodore D. Satterthwaite, MD, MA, assistant professor in the Department of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania. "Hopefully, one day such growth charts might allow us to identify abnormal brain development much earlier before it leads to major mental illness."

Studies on structural brain development have shown that puberty is an important source of sex differences. Previous work has shown that CBF declines throughout childhood, but the effects of puberty on properties of brain physiology such as CBF, also known as cerebral perfusion, are not well known. “We know that adult women have higher blood flow than men, but it was not clear when that difference began, so we hypothesized that the gap between women and men would begin in adolescence and coincide with puberty,” Satterthwaite says.

The Penn team imaged the brains of 922 youth ages 8 through 22 using arterial spin labeled (ASL) MRI. The youth were all members of the Philadelphia Neurodevelopmental Cohort, a National Institute of Mental Health-funded collaboration between the University of Pennsylvania Brain Behavior Laboratory and the Center for Applied Genomics at the Children’s Hospital of Philadelphia.

They found support for their hypothesis.

Age related differences were observed in the amount and location of blood flow in males versus females, with blood flow declining at a similar rate before puberty and diverging markedly in mid-puberty. At around age 16, while male CBF values continue to decline with advanced age, females CBF values actually increased. This resulted in females having notably higher CBF than males by the end of adolescence. The difference between males and females was most notable in parts of the brain that are critical for social behaviors and emotion regulation such as the orbitofrontal cortex. The researchers speculate that such differences could be related to females’ well-established superior performance on social cognition tasks. Potentially, these effects could also be related to the higher risk in women for depression and anxiety disorders, and higher risk of flat affect and schizophrenia in men.

Researchers reveal that neurons can utilize a supremely localized internal store of calcium to initiate the secretion of neuropeptides, one class of signaling molecules through which neurons communicate with each other and with other cells. The study appears in The Journal of General Physiology.

(Image caption: Localization of ryanodine receptors (red) in an isolated nerve terminal from the posterior pituitary gland. Image credit: McNally et al., 2014)

Neuropeptides are released from neurons through a process that—like other secretory events—is triggered primarily by the influx of calcium into the neuron through voltage-gated channels. Although neuropeptides are stored in large dense core vesicles (LDCVs) that also contain large amounts of calcium, it has been unclear whether these locally based calcium supplies can also be used to modulate secretion.

A team of researchers led by José Lemos from the University of Massachusetts Medical School examined the mechanisms at play during secretion of vasopressin from nerve terminals in the posterior pituitary gland, which releases the neuropeptide into the blood so that it can make its way to the kidney and regulate water retention. The researchers found that certain intracellular calcium channels known as ryanodine receptors are likely responsible for mobilizing calcium from LDCVs to facilitate vasopressin release. The findings indicate that neurons have a greater capacity than previously appreciated to fine-tune the release of neuropeptides and thereby their communications with other cells.

Research presented by Dr. Lynn Raymond, from the University of British Columbia, shows that blocking a specific class of glutamate receptors, called extrasynaptic NMDA receptors, can improve motor learning and coordination, and prevent cell death in animal models of Huntington disease. As Huntington disease is an inherited condition that can be detected decades before any clinical symptoms are seen in humans, a better understanding of the earliest changes in brain cell (neuronal) function, and the molecular pathways underlying those changes, could lead to preventive treatments that delay the onset of symptoms and neurodegeneration. “After more than a decade of research on the pre-symptomatic phase of Huntington disease, markers are being developed to facilitate assessment of interventional therapy in individuals carrying the genetic mutation for Huntington disease, before they become ill. This will make it possible to delay onset of disease,” says Dr. Raymond. These results were presented at the 2014 Canadian Neuroscience Meeting, the 8th annual meeting of the Canadian Association for Neuroscience - Association Canadienne des Neurosciences (CAN-ACN), held in Montreal, May 25-28.

The neurotransmitter glutamate has long been known to promote cell death, and its toxic effects occur through the action of a family of receptors known as the NMDARs (N-methyl-D-Aspartate ionotropic glutamate receptors). Unfortunately, treating disorders of the nervous system by blocking NMDARs has not been successful because such treatments have numerous side effects. A recent hypothesis based on work from many scientists suggests that NMDARs located in different regions at the surface of neurons may have opposite effects, which would explain why blocking all NMDARs is not a good treatment option. A synapse is a structure that allows one neuron to connect to another neuron and pass an electrical or chemical signal between them. Many receptors for neurotransmitters are located in synapses, as these are the main area where these chemical signals are transmitted. However, receptors can also be found outside the synapse, and in this case are called extra-synaptic receptors. Many recent studies have revealed that NMDARs located at synapses act to increase survival signaling and promote learning and memory, whereas extra-synaptic NMDARs shut off survival signaling, interfere with learning mechanisms, and increase cell death pathways.

Dr. Raymond and her team were able, by using a drug that selectively blocks extra-synaptic NMDARs early, before the appearance of any symptoms, to delay the onset of Huntington-like symptoms in a mouse model of the disease. These promising results could lead to new treatment avenues for Huntington patients, and delay the appearance of symptoms. “The drug we used, memantine, is currently being used to treat moderate-stage Alzheimer disease patients. Our results suggest that clinical studies of memantine and similarly-acting drugs in Huntington disease, particularly in the pre-symptomatic stage, are warranted,”says Dr. Raymond.

Extra-synaptic NMDARs have also been shown to be involved in other neurodegenerative diseases, such as Alzheimer disease, and in damage caused by traumatic brain injury and some forms of stroke. These results therefore suggest novel treatment avenues for many conditions in which neurons degenerate and die, a new way to protect neurons before the appearance of symptoms of neurodegeneration.