1. Seeing gene influencing performance of sleep-deprived people

    January 10, 2018 by Ashley

    From the Washington State University press release:

    Washington State University researchers have discovered a genetic variation that predicts how well people perform certain mental tasks when they are sleep deprived.

    Their research shows that individuals with a particular variation of the DRD2 gene are resilient to the effects of sleep deprivation when completing tasks that require cognitive flexibility, the ability to make appropriate decisions based on changing information.

    Sleep-deprived people with two other variations of the gene tend to perform much more poorly on the same kinds of tasks, the researchers found.

    The DRD2 dopamine receptor gene influences the processing of information in the striatum, a region of the brain that is known to be involved in cognitive flexibility.

    “Our work shows that there are people who are resilient to the effects of sleep deprivation when it comes to cognitive flexibility. Surprisingly these same people are just as affected as everyone else on other tasks that require different cognitive abilities, such as maintaining focus,” said Paul Whitney, a WSU professor of psychology and lead author of the study, which appeared in the journal Scientific Reports. “This confirms something we have long suspected, namely that the effects of sleep deprivation are not general in nature, but rather depend on the specific task and the genes of the person performing the task.”

    Why sleep loss affects us differently

    When deprived of sleep, some people respond better than others. Scientists have identified genes associated with this, but they have wondered why the effects of sleep loss tend to vary widely across both individuals and cognitive tasks. For example, after a day without sleep, some people might struggle with a reaction time test but perform well on decision-making tasks, or vice versa.

    In the current study, Whitney, along with colleagues John Hinson, WSU professor of psychology, and Hans Van Dongen, director of the WSU Sleep and Performance Research Center at WSU Spokane, compared how people with different variations of the DRD2 gene performed on tasks designed to test both their ability to anticipate events and their cognitive flexibility in response to changing circumstances.

    Forty-nine adults participated in the study at the WSU Spokane sleep laboratory. After a 10-hour rest period, 34 participants were randomly selected to go 38 hours without sleep while the other participants were allowed to sleep normally.

    Before and after the period of sleep deprivation, subjects were shown a series of letter pairings on a computer screen and told to click the left mouse button for a certain letter combination (e.g., an A followed by an X) and the right mouse button for all other letter pairs. After a while, both the sleep-deprived group and the rested group were able to identify the pattern and click correctly for various letter pairs.

    Then came the tricky part: in the middle of the task, researchers told the participants to now click the left mouse button for a different letter combination. The sudden switch confounded most of the sleep-deprived participants, but those who had a particular variation of the DRD2 gene handled the switch as well as they did when well-rested.

    “Our research shows this particular gene influences a person’s ability to mentally change direction when given new information,” Van Dongen said. “Some people are protected from the effects of sleep deprivation by this particular gene variation but, for most of us, sleep loss does something to the brain that simply prevents us from switching gears when circumstances change.”

    Training to cope with sleep loss

    Sleep deprivation’s effect on cognitive flexibility can have serious consequences, especially in high stakes, real-world situations like an emergency room or military operations where the ability to respond to changing circumstances is critical. For example, after a night without sleep, a surgeon might notice a spike in a patient’s vital signs midway through a procedure but be unable to use this information to decide on a better course of action.

    The WSU research team is currently applying what they learned from their study to develop new ways to help surgeons, police officers, soldiers and other individuals who regularly deal with the effects of sleep deprivation in critical, dynamic settings cope with the loss of cognitive flexibility.

    “Our long-term goal is to be able to train people so that no matter what their genetic composition is, they will be able to recognize and respond appropriately to changing scenarios, and be less vulnerable to sleep loss.” Whitney said. “Of course, the more obvious solution is to just get some sleep, but in a lot of real-world situations, we don’t have that luxury.”


  2. Study suggests food may affect mood – and differently depending on age

    December 25, 2017 by Ashley

    From the Binghamton University press release:

    Diet and dietary practices differentially affect mental health in young adults versus older adults, according to new research from Binghamton University, State University of New York.

    Lina Begdache, assistant professor of health and wellness studies at Binghamton University, along with fellow Binghamton researchers, conducted an anonymous internet survey, asking people around the world to complete the Food-Mood Questionnaire (FMQ), which includes questions on food groups that have been associated with neurochemistry and neurobiology. Analyzing the data, Begdache and Assistant Professor of Systems Science and Industrial Engineering Nasim Sabounchi found that mood in young adults (18-29) seems to be dependent on food that increases availability of neurotransmitter precursors and concentrations in the brain (meat). However, mood in mature adults (over 30 years) may be more reliant on food that increases availability of antioxidants (fruits) and abstinence of food that inappropriately activates the sympathetic nervous system (coffee, high glycemic index and skipping breakfast).

    “One of the major findings of this paper is that diet and dietary practices differentially affect mental health in young adults versus mature adults,” said Begdache. “Another noteworthy finding is that young adult mood appears to be sensitive to build-up of brain chemicals. Regular consumption of meat leads to build-up of two brain chemicals (serotonin and dopamine) known to promote mood. Regular exercise leads to build-up of these and other neurotransmitters as well. In other words, young adults who ate meat (red or white) less than three times a week and exercised less than three times week showed a significant mental distress.”

    “Conversely, mature adult mood seems to be more sensitive to regular consumption of sources of antioxidants and abstinence of food that inappropriately activates the innate fight-or-flight response (commonly known as the stress response),” added Begdache. “With aging, there is an increase in free radical formation (oxidants), so our need for antioxidants increases. Free radicals cause disturbances in the brain, which increases the risk for mental distress. Also, our ability to regulate stress decreases, so if we consume food that activates the stress response (such as coffee and too much carbohydrates), we are more likely to experience mental distress.”

    Begdache and her team are interested in comparing dietary intake between men and women in relation to mental distress. There is a gender difference in brain morphology which may be also sensitive to dietary components, and may potentially explain some the documented gender-specific mental distress risk, said Begdache.


  3. Study suggests restless sleep may be an early sign of Parkinson’s disease

    December 11, 2017 by Ashley

    From the Aarhus University press release:

    Researchers from Aarhus University have discovered that patients with the RBD sleep behaviour disorder lack dopamine and have a form of inflammation of the brain. This means that they are at risk of developing Parkinson’s disease or dementia when they grow older.

    Do you sleep restlessly and hit out and kick in your sleep? This could be a sign of a disorder associated with diseases of the brain. Researchers from Aarhus University have studied the condition of the dopamine producing nerve cells in the brain and cells that participate in the brain’s immune system in people suffering from the sleep disorder Rapid eye movement sleep behaviour disorder, RBD.

    The study shows that patients suffering from RBD have a risk of developing Parkinson’s disease or dementia in the future, because they already suffer from a lack of dopamine in the brain. Parkinson’s disease occurs precisely because the group of nerve cells in the brain that produce dopamine stop working.

    The RBD sleep disorder is characterised by disturbances in the part of sleep where dreams take place. Healthy people are relaxed and lie still during dream sleep, while people suffering from RBD live out their dreams so that while sleeping they can hit out, kick and shout.

    “These patients have an inflammation of the brain in the area where the dopamine-producing nerve cells are found,” says one of the researchers behind the study, Morten Gersel Stokholm from Aarhus University and the PET Centre at Aarhus University Hospital.

    The findings have just been published in the neurological journal The Lancet Neurology.

    This is completely new knowledge, as researchers have not previously demonstrated that there is a form of inflammation of the brain in patients who are at risk of developing Parkinson’s disease.

    “With this study, we have gained new knowledge about the disease processes in the brain in the early initial stages of the disease development. The idea is for this knowledge to be used to determine which patients with the sleep disorder will later develop Parkinson’s disease. At the same time, this is also knowledge that can help to develop drugs which can stop or slow the development of the diseases,” explains Morten Gersel Stokholm about the sleep disorder which most often affects persons aged 50-70, and more frequently men than women.

    Parkinson’s disease

    There are 7,300 Parkinson’s disease patients in Denmark. Symptoms are slow movements, often with shaking, together with muscular rigidity. Parkinson’s disease is a chronic condition that continues to worsen over time. The disease is somewhat more common in men than in women. Parkinson’s disease occurs because the brain lacks dopamine. It is primarily adults who are affected, and the first signs most often appear between the ages of 50-70.

    Background for the results:

    The study is a case-control study.

    The people behind the project are Medical Doctor and PhD student Morten Gersel Stokholm and Associate Professor, MD, Nicola Pavese in collaboration with medical doctors from the Department of Neurology and the Sleep Clinic, Aarhus University Hospital and medical doctors from the University Hospital Clinic de Barcelona.


  4. Higher estrogen levels linked to increased alcohol sensitivity in brain’s ‘reward center’

    November 14, 2017 by Ashley

    From the University of Illinois at Chicago press release:

    The reward center of the brain is much more attuned to the pleasurable effects of alcohol when estrogen levels are elevated, an effect that may underlie the development of addiction in women, according to a study on mice at the University of Illinois at Chicago.

    Led by Amy Lasek, assistant professor of psychiatry in the UIC College of Medicine, researchers found that neurons in a region of the brain called the ventral tegmental area, or VTA (also known as the “reward center”), fired most rapidly in response to alcohol when their estrogen levels were high. This response, according to their findings published online in the journal PLOS ONE, is mediated through receptors on dopamine-emitting neurons in the VTA.

    “When estrogen levels are higher, alcohol is much more rewarding,” said Lasek, who is the corresponding author on the paper and a researcher in the UIC Center for Alcohol Research in Epigenetics. “Women may be more vulnerable to the effects of alcohol or more likely to overindulge during certain stages of their cycle when estrogen levels are higher, or may be more likely to seek out alcohol during those stages.”

    Studies indicate that gender differences in psychiatric disorders, including addiction, are influenced by estrogen, one of the primary female sex hormones. Women are more likely to exhibit greater escalation of abuse of alcohol and other drugs, and are more prone to relapse in response to stress and anxiety.

    The VTA helps evaluate whether something is valuable or good. When neurons in this area of the brain are stimulated, they release dopamine — a powerful neurotransmitter responsible for feelings of wellness — and, in large doses, euphoria. When something good is encountered — for example, chocolate — the neurons in the VTA fire more rapidly, enforcing reward circuitry that encodes the idea that chocolate is enjoyable and something to be sought out. Over time, the VTA neurons fire more quickly at the sight, or even thought of, chocolate, explained Lasek. In addiction, VTA neurons are tuned into drugs of abuse, and fire more quickly in relation to consuming or even thinking about drugs, driving the person to seek them out — often at the expense of their own health, family, friends and jobs.

    Many animal studies have shown that alcohol increases the firing of dopamine-sensitive neurons in the VTA, but little is known about exactly why this occurs.

    Lasek and her colleagues examined the relationship between estrogen, alcohol and the VTA in female mice. They used naturally cycling mice that were allowed to go through their normal estrous cycles, akin to the menstrual cycle in women.

    Mice were evaluated to determine when they entered diestrus — the phase in the estrous cycle when estrogen levels are close to their peak.

    “In mice in diestrus, estrogen levels increase to about 10 times higher than they are in estrus, the phase in which ovulation occurs and estrogen levels drop,” Lasek said.

    VTAs were taken from mice in both estrus and diestrus and kept alive in special chambers. Electrodes recorded the activity of individual dopamine-sensitive neurons in the VTA. Next, the researchers added alcohol to the chamber. Activity increased twice as much in neurons from mice in diestrus compared to the response of neurons from mice in estrus.

    Lasek and her colleagues then blocked estrogen receptors on dopamine-sensitive neurons in VTA in mice in estrus and diestrus. With the blocker present, the response to alcohol in neurons from mice in diestrus was significantly lower compared with neurons where estrogen receptors remained functional. The estrogen receptor blocker reduced the alcohol response to levels seen in mice in estrus. The responses to alcohol in neurons from mice in estrus were unaffected by the estrogen receptor blocker.

    “The increased reward response to alcohol we see when estrogen levels are high is mediated through receptors for estrogen in the VTA,” said Mark Brodie, professor of physiology and biophysics in the UIC College of Medicine and a co-author on the paper.

    Lasek believes that the increased sensitivity to alcohol in the VTA when estrogen levels peak may play a significant role in the development of addiction in women.

    “We already know that binge drinking can lead to lasting changes in the brain, and in women, those changes may be faster and more significant due to the interaction we see between alcohol, the VTA and estrogen,” Lasek said. “Binge drinking can increase the risk of developing alcoholism, so women need to be careful about how much alcohol they drink. They should be aware that they may sometimes inadvertently over-consume alcohol because the area of the brain involved in alcohol reward is responding very strongly.”


  5. Study links herbicide to Parkinson’s disease

    October 30, 2017 by Ashley

    From the Northwestern University press release:

    Northwestern Medicine scientists have used an innovative gene editing technique to identify the genes that may lead to Parkinson’s disease after exposure to paraquat, a commonly-used herbicide.

    This study, which utilized the CRISPR-Cas9 gene-editing tool, serves as a proof-of-concept for using genetic screens to investigate the biology of oxidative stress, according to senior author Navdeep Chandel, PhD, the David W. Cugell, MD, Professor of Medicine in the Division of Pulmonary and Critical Care at Northwestern University Feinberg School of Medicine.

    The study was published in Nature Chemical Biology and the first author was Colleen Reczek, PhD, a postdoctoral fellow in Chandel’s lab. Other authors included Chandel lab members Hyewon Kong, a student in the Walter S. and Lucienne Driskill Graduate Program in Life Sciences, and Inmaculada Martinez-Reyes, PhD, a postdoctoral fellow.

    The use of paraquat, which causes cell death via oxidative stress, is restricted in the United States and banned in the European Union, but the chemical is still used widely throughout Asia and the developing world, according to Chandel, also a professor of Cell and Molecular Biology. Ingestion of paraquat can lead to lung fibrosis or even death, but a 2011 study linked occupational use to an increased risk for Parkinson’s disease, renewing interest in its impact on humans.

    A major cause of Parkinson’s is the loss of function in dopamine neurons in a small brain region called the substantia nigra pars compacta, according to previous research. Those neurons are known to be highly vulnerable to oxidative stress, leading scientists to hypothesize paraquat was linked to Parkinson’s disease through this oxidative stress.

    “Paraquat generates a lot of oxidants. Naturally those dopaminergic neurons will be the most susceptible to damage,” Chandel said.

    However, the mechanism by which paraquat created oxidants was unknown — until now.

    Chandel and his collaborators conducted a CRISPR-Cas9 positive-selection screen, creating thousands of cells, each with one individual gene turned off.

    “We thought it was a metabolic protein that paraquat was activating to generate oxidants,” Chandel said. “So we localized our work to the 3,000 genes that encode for metabolic proteins, rather than the 18,000 to 20,000 genes human cells have in total.”

    They exposed that subset of cells to paraquat — the majority of cells died, but not all of them. Certain cells with knocked-out genes were resistant to paraquat, suggesting those genes may be responsible for the toxicity.

    Scientists identified three genes whose loss conferred resistance to paraquat: POR, ATP7A and SLC45A4. POR, a protein in the endoplasmic reticulum, was fingered as the main source of oxidation that caused the damage. Pinpointing these genes could help identify people who are especially vulnerable to paraquat, Chandel said.

    “Certain people with genetic mutations could have high levels of this gene. They would be very susceptible to paraquat poisoning while working on a farm, for example,” he said.

    However, the most impactful takeaway from the paper may be as a proof-of-concept for investigative biology of oxidative stress, according to Chandel.

    POR had been previously implicated in oxidant generation, but the majority of evidence had pointed to systems in the mitochondria, according to the study, and no definitive answer had emerged until this study was conducted.

    “Now, we can go in and test how agents of oxidant stress work,” Chandel said. “The beauty of the paper is in the power of these unbiased genetic screens we can now use with CRISPR technology.”

    Investigating oxidant stress could pay dividends in the future, according to Chandel, including in the development of drugs designed to generate oxidative stress in cancer cells, killing them while leaving healthy cells alone. While some drugs currently exist, not enough is known about their pathways to create a functioning compound, Chandel said.

    “The biology of oxidative stress is still a mystery,” he said. “CRISPR positive-selection screens could be a way to figure it out.”


  6. How dopamine tells you it isn’t worth the wait

    October 23, 2017 by Ashley

    From the University of Texas at San Antonio press release:

    How do we know if it was worth the wait in line to get a meal at the new restaurant in town? To do this our brain must be able to signal how good the meal tastes and associate this feeling with the restaurant. This is done by a small group of cells deep in the brain that release the chemical dopamine. The amount of dopamine released by these cells can influence our decisions by telling us how good a reward will be in the future. For example, more dopamine is released to the smell of a cake baking relative to the smell of leftovers. But does waiting change how dopamine is released?

    A new study in Cell Reports by Matthew Wanat, assistant professor of biology at The University of Texas at San Antonio (UTSA), sheds light on how dopamine cells in the brain signal the passage of time. Wanat’s study used a technique called voltammetry to record dopamine release in rodents trained using Pavlovian conditioning. This task used two different tones that both predicted the delivery of a food reward. One tone was presented only after a short wait while the other tone was presented only after a long wait. Wanat and colleagues found that more dopamine was released to the short wait tone. These results highlight that when dopamine neurons respond to cues, faster is better.

    “The big question that we’re focusing on is to identify the brain signals that influence the decisions we make,” Wanat said. “Many decisions are based upon comparing the value between cues associated with different rewards. There is a lot of evidence to suggest that these dopamine signals and external cues provide useful value-related signals that could inform our decisions to engage in a behavior.”

    While Wanat and his collaborators are interested in studying how dopamine release is involved with cues triggering behavior, their work could also inform the understanding of drug addiction, which is closely intertwined with dopamine. Drug addiction can “hijack” the brain regions where dopamine is released. “By figuring out how the dopamine system works in normal and abnormal circumstances, we could potentially identify important changes and the ways that could target the dopamine system to rectify the consequences of those behaviors,” Wanat said.

    “A lot has been said about the role of dopamine in reward, but reward is only really important in the context of making choices. Dr. Wanat’s experiments allow direct measurement of dopamine acting in the brain during the process of choosing, and reveals how the brain decides the values of our choices,” said Charles Wilson, Ewing Halsell Distinguished Chair in Biology.

    Wanat’s overarching research focuses on the brain’s relationships with memory, stress and drug addiction and how those components interact with each other. He is a member of the UTSA Neurosciences Institute, a multidisciplinary research organization for integrated brain studies with the mission to foster a collaborative community of scientists committed to studying the biological basis of human experience and behavior and the origin and treatment of nervous system diseases.

    Wanat is one of 40 brain health researchers at UTSA, a group that includes experts in neurodegenerative disease, brain circuits and electrical signaling, traumatic brain injury, regenerative medicine, stem cell therapies, medicinal chemistry, neuroinflammation, drug design and psychology. Together, they are collaborating on complex, large-scale research producing a greater understanding of the brain’s complexity and the factors that cause its decline.


  7. Study examines effect of oxytocin on sociability

    October 8, 2017 by Ashley

    From the Stanford University Medical Center press release:

    Why is it so much fun to hang out with our friends? Why are some people so sociable while others are loners or seemingly outright allergic to interactions with others?

    A new study by researchers at the Stanford University School of Medicine begins to provide an answer, pinpointing places and processes in the brain that promote socialization by providing pleasurable sensations when it occurs. The findings point to potential ways of helping people, such as those with autism or schizophrenia, who can be painfully averse to socializing.

    The study, which will be published Sept. 29 in Science, details the role of a substance called oxytocin in fostering and maintaining sociability. The senior author is Robert Malenka, MD, PhD, professor and associate chair of psychiatry and behavioral science. The lead author is former postdoctoral scholar Lin Hung, PhD.

    “Our study reveals new insights about the brain circuitry behind social reward, the positive experience you often get when you run into an old friend or meet somebody you like,” said Malenka, who has focused much of his research on an assembly of interacting nerve tracts in the brain collectively known as the reward circuitry.

    “The reward circuitry is crucial to our survival because it rewards us for doing things that have, during our evolutionary history, tended to enhance our survival, our reproduction and the survival of our resulting offspring,” said Malenka, who holds the Nancy Friend Pritzker Professorship in Psychiatry and the Behavioral Sciences. “It tells us what’s good by making us feel good. When you’re hungry, food tastes great. When you’re thirsty, water is refreshing. Sex is great pretty much most of the time. Hanging out with your friends confers a survival advantage, too, by decreasing your chances of getting eaten by predators, increasing your chances of finding a mate and maybe helping you learn where food and water are.”

    Reward system conserved over evolution

    Because the reward system is so critical, it’s been carefully conserved over evolution and in many respects operates just the same way in mice as it does in humans, making mice good experimental models for studying it.

    Far and away the most important component of the brain’s reward circuitry, Malenka said, is a nerve tract that runs from a structure deep in the brain called the ventral tegmental area to a midbrain structure called the nucleus accumbens. The ventral tegmental area houses a cluster of nerve cells, or neurons, whose projections to the nucleus accumbens secrete a substance called dopamine, altering neuronal activity in this region. Dopamine release in the nucleus accumbens can produce a wave of pleasure, telling the brain that the event going on is helpful for survival. Dopamine release in this region, and subsequent changes in activity there and in downstream neurons, also prime the brain to remember the events and the behaviors leading up to the chemical’s release.

    This tract, so famous for reinforcing survival-enhancing behaviors such as eating, drinking and mating, has been infamously implicated in our vulnerability to drug addiction — a survival-threatening outcome resulting from drugs’ ability to inappropriately stimulate dopamine secretion in the tract. But understanding exactly how and under what natural conditions the firing of its dopamine-secreting nerves gets tripped off is a work in progress.

    Earlier research has specifically implicated dopamine release in the nucleus accumbens in social behavior. “So, we knew reward circuitry plays a role in social interactions,” Malenka said. “What we still didn’t know — but now we do — was: How does this increased dopamine release during social interaction come about?”

    ‘Love hormone’ pulls the strings

    It turns out that another chemical — oxytocin — is pulling the strings.

    Oxytocin is sometimes called the “love hormone” because it’s thought to be involved in falling in love, mother-child bonding and female sexual arousal, as well as lifetime pair-bonding of sexual mates among some species. The chief source of oxytocin in the brain is the paraventricular nucleus, which resides in a deep-brain structure called the hypothalamus that serves as a manifold master regulator of body temperature, hunger, thirst, sleep, emotional reactions and more.

    Research over the last 20 to 40 years has suggested that oxytocin plays a role in promoting not just sexual or nurturing behavior, but also sociability. A 2013 study co-authored by Malenka showed that oxytocin was essential to reinforcing friendly, social behavior in mice. But how that occurred was unclear, as the paraventricular nucleus sends oxytocin-squirting nerve tracts to many areas throughout the brain.

    So Malenka and his colleagues designed experiments to nail down oxytocin’s role in social behavior. They confirmed that a tract running from the paraventricular nucleus to the ventral tegmental area carried oxytocin. They showed, for the first time, that activity in this tract’s oxytocin-secreting neurons jumped during mice’s social interactions and that this neuronal activity was required for their normal social behavior. Disrupting this activity inhibited sociability but didn’t impair the mice’s movement or their appetite for pleasurable drugs, such as cocaine.

    The researchers demonstrated that oxytocin secreted in the ventral tegmental area by neurons originating in the paraventricular nucleus fosters sociability by binding to receptors on the dopamine-secreting neurons that compose the tract running from the ventral tegmental area to the nucleus accumbens, enhancing the firing of the reward-circuit tract.

    The findings should help translational researchers develop medications for individuals with neurological disorders, such as autism, depression and schizophrenia, whose conditions compromise their ability to experience pleasure from connecting with other people, Malenka said.

    But he also voiced a desire for more widespread applications of the research. “With so much hatred and anger in the world,” he said, “what could possibly be more important than understanding the mechanisms in the brain that make us want to be friendly with other people?”


  8. Study finds ingredient in malted barley that stimulates reward centre in brain

    October 6, 2017 by Ashley

    From the Friedrich-Alexander-Universität Erlangen-Nürnberg press release:

    Visitors to the Oktoberfest have always known it and now it has been scientifically proven — beer can lift your spirits. Scientists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) examined 13,000 food components to find out whether they stimulate the reward centre in the brain and make people feel good. Hordenine which is found in malted barley and beer seems to do the job quite well.

    Some foods make us happy. Well, maybe not happy but they make us feel good. That is why we cannot stop eating when we have had enough. Scientists call this hedonic hunger — the drive to eat for pleasure rather than to satisfy an actual biological need. This feel-good effect is caused by the neurotransmitter dopamine — tempting foods stimulate the reward centre in the brain where the dopamine D2 receptor is located. Researchers of the Chair of Food Chemistry at FAU investigated whether there are special substances in foods that activate the dopamine D2 receptor in the same way as dopamine.

    The team worked with FAU’s Computer Chemistry Centre using a virtual screening approach which is often used in pharmaceutical research. This process analyses food components in a computer simulation rather than in the laboratory. Using computer simulations means that all types of known substance can be investigated. In the laboratory, it is only feasible to test a small selection of foodstuff extracts using standard screening techniques.

    13,000 molecules, 17 hits

    Initially, the scientists set up a database of 13,000 molecules which are present in foodstuffs. Using this database, the objective was to find those molecules that fit the dopamine D2 receptor — rather like finding the right key for a lock. The system was then used to identify which molecules could interact with the dopamine D2 receptor; these might be present in synthetic substances already known to interact with the receptor, such as medicines for treating Parkinson’s and schizophrenia, or which might be candidates for interaction due to the three-dimensional structure of the receptor. In the end, 17 of the original 13,000 options were selected and these were analysed in the laboratory in cooperation with the Division of Medicinal Chemistry at FAU.

    Beer — a surprise finding

    The most promising results were obtained for hordenine, a substance present in malted barley and beer. ‘It came as a bit of surprise that a substance in beer activates the dopamine D2 receptor, especially as we were not specifically looking at stimulant foodstuffs,’ explains Prof. Dr. Monika Pischetsrieder.

    Just like dopamine, hordenine stimulates the dopamine D2 receptor, however it uses a different signalling pathway. In contrast with dopamine, hordenine activates the receptor solely through G proteins, potentially leading to a more prolonged effect on the reward centre of the brain. The team is now investigating whether hordenine levels in beer are sufficient to have a significant effect on the reward centre. All things considered, the results indicate that hordenine may well contribute to the mood-boosting effect of beer.


  9. Neurons that control brain’s body clock identified

    August 18, 2017 by Ashley

    From the University of Virginia press release:

    Neurons in the brain that produce the pleasure-signaling neurotransmitter dopamine also directly control the brain’s circadian center, or “body clock” — the area that regulates eating cycles, metabolism and waking/resting cycles — a key link that possibly affects the body’s ability to adapt to jet lag and rotating shift work, a new University of Virginia study has demonstrated.

    The finding is reported in today’s online edition of the journal Current Biology.

    “This discovery, which identifies a direct dopamine neuron connection to the circadian center, is possibly the first step toward the development of unique drugs, targeting specific neurons, to combat the unpleasant symptoms of jet-lag and shiftwork, as well as several dangerous pathologies,” said Ali Deniz Güler, a UVA professor of biology and neuroscience who oversaw the study in his lab.

    Modern society often places abnormal pressure on the human body — from shifting time schedules due to air travel, to work cycles that don’t conform to natural light, to odd eating times — and these external conditions create an imbalance in the body’s natural cycles, which are evolutionarily synchronized to day and night. These imbalances may contribute to depression, obesity, cardiovascular diseases and even cancer.

    “Scientists have been working for decades to help the body’s circadian system readily re-synchronize to variable work and eating schedules and flights across multiple time zones,” Güler said. “Finding this connection between dopamine-producing neurons and the circadian center allows us to target these neurons with therapies that could potentially provide relief of symptoms for travelers and shift workers particularly, and possibly people with insomnia.”

    Sleep disorders and abnormal circadian rhythms affecting the brain and other organs can worsen many pathologies involving aberrant dopamine neurotransmission, Güler said, including Parkinson’s disease, depression, attention deficit/hyperactivity disorder, bipolar disorder, schizophrenia and drug addiction.

    “New understanding of dopamine-producing neurons and the connection to the body’s biorhythms may go a long way toward treatments to alleviate the harmful effects of these serious pathologies,” Güler said.

    Güler’s laboratory specializes in identifying neural circuits that govern biological rhythms in the brain, providing unique therapeutic targets for a range of diseases. Ph.D. candidate Ryan Grippo, Güler’s graduate student, led the Current Biology study.

    The researchers used two types of mice in their investigation: one normal, the other with dopamine signaling disrupted. By shifting the light schedules of the two groups by six hours, a jet-lag effect, they found that the dopamine-disrupted animals took much longer to resynchronize to the six-hour time shift, indicating feedback between the dopamine neurons and the circadian center.

    “This shows that when we engage in rewarding activities like eating, we are inadvertently affecting our biological rhythms,” Güler said. “We may have found the missing link to how pleasurable things and the circadian system influence one another.”


  10. Why does prenatal alcohol exposure increase the likelihood of addiction?

    July 21, 2017 by Ashley

    From the University at Buffalo press release:

    One of the many negative consequences when fetuses are exposed to alcohol in the womb is an increased risk for drug addiction later in life. Neuroscientists in the University at Buffalo Research Institute on Addictions are discovering why.

    Through a research grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH), Senior Research Scientist Roh-Yu Shen, PhD, is studying how prenatal alcohol exposure alters the reward system in the brain and how this change continues through adulthood.

    The key appears to lie with endocannibinoids, cannabis-like chemicals that are produced by the brain itself.

    “By understanding the role endocannibinoids play in increasing the brain’s susceptibility to addiction, we can start developing drug therapies or other interventions to combat that effect and, perhaps, other negative consequences of prenatal alcohol exposure,” Shen says.

    Prenatal alcohol exposure is the leading preventable cause of birth defects and neurodevelopmental abnormalities in the United States. Fetal Alcohol Spectrum Disorders (FASD) cause cognitive and behavioral problems. In addition to increased vulnerability of alcohol and other substance use disorders, FASD can lead to other mental health issues including Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety and problems with impulse control.

    After the prenatal brain is exposed to alcohol, the endocannibinoids have a different effect on certain dopamine neurons which are involved in addicted behaviors than when brain is not exposed to alcohol,” Shen says. “The end result is that the dopamine neurons in the brain become more sensitive to a drug of abuse’s effect. So, later in life, a person needs much less drug use to become addicted.”

    Specifically, in the ventral tegmental area (VTA) of the brain, endocannibinoids play a significant role in weakening the excitatory synapses onto dopamine neurons. The VTA is the part of the brain implicated in addiction, attention and reward processes. However, in a brain prenatally exposed to alcohol, the effect of the endocannabinoids is reduced due to a decreased function of endocannabinoid receptors. As a result, the excitatory synapses lose the ability to be weakened and continue to strengthen, which Shen believes is a critical brain mechanism for increased addiction risk.