Posts tagged anxiety
Articles and news from the latest research reports.
Glowing Worms Illuminate Roots of Behavior
A research team at Worcester Polytechnic Institute (WPI) and The Rockefeller University in New York has developed a novel system to image brain activity in multiple awake and unconstrained worms. The technology, which makes it possible to study the genetics and neural circuitry associated with animal behavior, can also be used as a high-throughput screening tool for drug development targeting autism, anxiety, depression, schizophrenia, and other brain disorders.
Image: Neurons in the worms (marked by arrows) glow as the animals sense attractive odors.
The team details their technology and early results in the paper “High-throughput imaging of neuronal activity in Caenorhabditis elegans,” published on-line in advance of print by the journal Proceedings of the National Academy of Sciences.
"One of our major objectives is to understand the neural signals that direct behavior—how sensory information is processed through a network of neurons leading to specific decisions and responses," said Dirk Albrecht, PhD, assistant professor of biomedical engineering at WPI and senior author of the paper. Albrecht led the research team both at WPI and at Rockefeller, where he served previously as a postdoctoral researcher in the lab of Cori Bargmann, PhD, a Howard Hughes Medical Institute Investigator and a co-author of the new paper.
To study neuronal activity, Albrecht’s lab uses the tiny worm Caenorhabditis elegans (C. elegans), a nematode found in many environments around the world. A typical adult C. elegans is just 1 millimeter long and has 969 cells, of which 302 are neurons. Despite its small size, the worm is a complex organism able to do all of the things animals must do to survive. It can move, eat, mate, and process environmental cues that help it forage for food or react to threats. As a bonus for researchers, C.elegans is transparent. By using various imaging technologies, including optical microscopes, one can literally see into the worm and watch physiological processes in real time.
Numerous studies have been done by “worm labs” around the world exploring various neurological processes in C. elegans. These have typically been done using one worm at a time, with the animal’s body fixed in place on a slide. In their new paper, Albrecht’s team details how they imaged, recorded, and analyzed specific neurons in multiple animals as they wormed their way around a custom-designed microfluidic array, called an arena, where they were exposed to favorable or hostile sensory cues.
Specifically, the team engineered a strain of worms with neurons near the head that would glow when they sensed food odors. In experiments involving up to 23 worms at a time, Albrecht’s team infused pulses of attractive or repulsive odors into the arena and watched how the worms reacted. In general, the worms moved towards the positive odors and away from the negative odors, but the behaviors did not always follow this pattern. “We were able to show that the sensory neurons responded to the odors similarly in all the animals, but their behavioral responses differed significantly,” Albrecht said. “These animals are genetically identical, and they were raised together in the same environment, so where do their different choices come from?”
In addition to watching the head neurons light up as they picked up odor cues, the new system can trace signaling through “interneurons.” These are pathways that connect external sensors to the rest of the network (the “worm brain”) and send signals to muscle cells that adjust the worm’s movement based on the cues. Numerous brain disorders in people are believed to arise when neural networks malfunction. In some cases the malfunction is dramatic overreaction to a routine stimulus, while in others it is a lack of appropriate reactions to important cues. Since C. elegans and humans share many of the same genes, discovering genetic causes for differing neuronal responses in worms could be applicable to human physiology. Experimental compounds designed to modulate the action of nerve cells and neuronal networks could be tested first on worms using Albrecht’s new system. The compounds would be infused in the worm arena, along with other stimuli, and the reaction of the worms’ nervous systems could be imaged and analyzed.
"The basis of our work is to combine biomedical engineering and neuroscience to answer some of these fundamental questions and hopefully gain insight that would be beneficial for understanding and eventually treating human disorders," Albrecht said.
(Source: wpi.edu)
Studies pinpoint specific brain areas and mechanisms associated with depression and anxiety
Research released today reveals new mechanisms and areas of the brain associated with anxiety and depression, presenting possible targets to understand and treat these debilitating mental illnesses. The findings were presented at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.
More than 350 million people worldwide suffer from clinical depression and between 5 and 25 percent of adults suffer from generalized anxiety, according to the World Health Organization. The resulting emotional and financial costs to people, families, and society are significant. Further, antidepressants are not always effective and often cause severe side effects.
Today’s new findings show that:
- A molecule in the immune system may contribute to depression, suggesting a potential biomarker for the disease (Georgia Hodes, PhD, abstract 542.1, see attached summary).
- Decreasing a chemical signal in the amygdala, a brain area associated with emotional processing, produces antidepressant-like effects in mice (Yann Mineur, PhD, abstract 504, see attached summary).
- MicroRNAs, tiny molecules that alter gene expression, correlate with how mice respond to socially stressful situations that cause depressive-like behavior. The findings may help determine why some people are more likely to suffer from depression than others (Karen Scott, PhD, abstract 731.2, see attached summary).
Other recent findings discussed show that:
- A pathway between two brain regions, the amygdala and the hippocampus, plays a significant role in anxiety. Shutting down this connection can decrease anxiety-like behavior in mice (Ada Felix-Ortiz, MS, presentation 393.01, see attached speaker summary).
- Aversive experiences can change how humans, particularly those with anxiety disorders, perceive stimuli. After a severe negative incident, patients with anxiety disorders over-generalize the experience and have increased emotional responses to subsequent similar situations (Rony Paz, PhD, presentation 295.05, see attached speaker summary).
“Today’s findings represent our rapidly growing understanding of the individual molecules and brain circuits that may contribute to depression and anxiety,” said press conference moderator Lisa Monteggia, PhD, of the University of Texas Southwestern Medical Center, an expert on mechanisms of antidepressant action. “These exciting discoveries represent the potential for significant changes in how we diagnose and treat these illnesses that touch millions.”
Personal reflection triggers increased brain activity during depressive episodes
Research by the University of Liverpool has found that people experiencing depressive episodes display increased brain activity when they think about themselves.
Using functional magnetic resonance imaging (fMRI) brain imaging technologies, scientists found that people experiencing a depressive episode process information about themselves in the brain differently to people who are not depressed.
British Queen
Researchers scanned the brains of people in major depressive episodes and those that weren’t whilst they chose positive, negative and neutral adjectives to describe either themselves or the British Queen - a figure significantly removed from their daily lives but one that all participants were familiar with.
Professor Peter Kinderman, Head of the University’s Institute of Psychology, Health and Society, said: “We found that participants who were experiencing depressed mood chose significantly fewer positive words and more negative and neutral words to describe themselves, in comparison to participants who were not depressed.
“That’s not too surprising, but the brain scans also revealed significantly greater blood oxygen levels in the medial superior frontal cortex – the area associated with processing self-related information – when the depressed participants were making judgments about themselves.
“This research leads the way for further studies into the psychological and neural processes that accompany depressed mood. Understanding more about how people evaluate themselves when they are depressed, and how neural processes are involved could lead to improved understanding and care.”
Dr May Sarsam, from the Mersey Care NHS Trust, said: “This study explored the difference in medical and psychological theories of depression. It showed that brain activity only differed when depressed people thought about themselves, not when they thought about the Queen or when they made other types of judgements, which fits very well with the current psychological theory.
Equally important
“Thought and neurochemistry should be considered as equally important in our understanding of mental health difficulties such as depression.”
Depression is associated with extensive negative feelings and thoughts. Nearly one-fifth of adults experience anxiety or depression, with the conditions affecting a higher proportion of women than men.
The research, in collaboration with the Mersey Care NHS Trust and the Universities of Manchester, Edinburgh and Lancaster, is published in PLOS One.
Neuroscientists Determine How Treatment for Anxiety Disorders Silences Fear Neurons
Excessive fear can develop after a traumatic experience, leading to anxiety disorders such as post-traumatic stress disorder and phobias. During exposure therapy, an effective and common treatment for anxiety disorders, the patient confronts a fear or memory of a traumatic event in a safe environment, which leads to a gradual loss of fear. A new study in mice, published online today in Neuron, reports that exposure therapy remodels an inhibitory junction in the amygdala, a brain region important for fear in mice and humans. The findings improve our understanding of how exposure therapy suppresses fear responses and may aid in developing more effective treatments. The study, led by researchers at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts, was partially funded by a New Innovator Award from the Office of the Director at the National Institutes of Health.
A fear-inducing situation activates a small group of neurons in the amygdala. Exposure therapy silences these fear neurons, causing them to be less active. As a result of this reduced activity, fear responses are alleviated. The research team sought to understand how exactly exposure therapy silences fear neurons.
The researchers found that exposure therapy not only silences fear neurons but also induces remodeling of a specific type of inhibitory junction, called the perisomatic synapse. Perisomatic inhibitory synapses are connections between neurons that enable one group of neurons to silence another group of neurons. Exposure therapy increases the number of perisomatic inhibitory synapses around fear neurons in the amygdala. This increase provides an explanation for how exposure therapy silences fear neurons.
“The increase in number of perisomatic inhibitory synapses is a form of remodeling in the brain. Interestingly, this form of remodeling does not seem to erase the memory of the fear-inducing event, but suppresses it,” said senior author, Leon Reijmers, Ph.D., assistant professor of neuroscience at Tufts University School of Medicine and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.
Reijmers and his team discovered the increase in perisomatic inhibitory synapses by imaging neurons activated by fear in genetically manipulated mice. Connections in the human brain responsible for suppressing fear and storing fear memories are similar to those found in the mouse brain, making the mouse an appropriate model organism for studying fear circuits.
Mice were placed in a box and experienced a fear-inducing situation to create a fear response to the box. One group of mice, the control group, did not receive exposure therapy. Another group of mice, the comparison group, received exposure therapy to alleviate the fear response. For exposure therapy, the comparison group was repeatedly placed in the box without experiencing the fear-inducing situation, which led to a decreased fear response in these mice. This is also referred to as fear extinction.
The researchers found that mice subjected to exposure therapy had more perisomatic inhibitory synapses in the amygdala than mice who did not receive exposure therapy. Interestingly, this increase was found around fear neurons that became silent after exposure therapy.
“We showed that the remodeling of perisomatic inhibitory synapses is closely linked to the activity state of fear neurons. Our findings shed new light on the precise location where mechanisms of fear regulation might act. We hope that this will lead to new drug targets for improving exposure therapy,” said first author, Stéphanie Trouche, Ph.D., a former postdoctoral fellow in Reijmers’ lab at Tufts and now a medical research council investigator scientist at the University of Oxford in the United Kingdom.
“Exposure therapy in humans does not work for every patient, and in patients that do respond to the treatment, it rarely leads to a complete and permanent suppression of fear. For this reason, there is a need for treatments that can make exposure therapy more effective,” Reijmers added.
(Source: now.tufts.edu)
Research Finds Pain In Infancy Alters Response To Stress, Anxiety Later In Life
Early life pain alters neural circuits in the brain that regulate stress, suggesting pain experienced by infants who often do not receive analgesics while undergoing tests and treatment in neonatal intensive care may permanently alter future responses to anxiety, stress and pain in adulthood, a research team led by Dr. Anne Murphy, associate director of the Neuroscience Institute at Georgia State University, has discovered.
An estimated 12 percent of live births in the U.S. are considered premature, researchers said. These infants often spend an average of 25 days in neonatal intensive care, where they endure 10-to-18 painful and inflammatory procedures each day, including insertion of feeding tubes and intravenous lines, intubation and repeated heel lance. Despite evidence that pain and stress circuitry in the brain are established and functional in preterm infants, about 65 percent of these procedures are performed without benefit of analgesia. Some clinical studies suggest early life pain has an immediate and long-term impact on responses to stress- and anxiety-provoking events.
The Georgia State study examined whether a single painful inflammatory procedure performed on male and female rat pups on the day of birth alters specific brain receptors that affect behavioral sensitivity to stress, anxiety and pain in adulthood. The findings demonstrated that such an experience is associated with site-specific changes in the brain that regulate how the pups responded to stressful situations. Alterations in how these receptors function have also been associated with mood disorders.
The study findings mirror what is now being reported clinically. Children who experienced unresolved pain following birth show reduced responsiveness to pain and stress.
“While a dampened response to painful and stressful situations may seem advantageous at first, the ability to respond appropriately to a potentially harmful stimulus is necessary in the long term,” Dr. Murphy said.
“The fact that less than 35 percent of infants undergoing painful and invasive procedures receive any sort of pre- or post-operative pain relief needs to be re-evaluated in order to reduce physical and mental health complications associated with preterm birth.”
Individuals Genetically Predisposed to Anxiousness May Be Less Likely to Volunteer and Help Others
Scientists increasingly are uncovering answers for human behavior through genetic research. Now, a University of Missouri researcher has found that prosocial behavior, such as volunteering and helping others, is related to the same gene that predisposes individuals to anxiety disorders. Helping such individuals cope with their anxiety may increase their prosocial behavior, the researcher said.
“Prosocial behavior is linked closely to strong social skills and is considered a marker of individuals’ health and well-being,” said Gustavo Carlo, Millsap Professor of Diversity in MU’s College of Human Environmental Sciences. “Social people are more likely to be healthier, excel academically, experience career success and develop deeper interpersonal relationships that may help alleviate stress.”
Carlo and his colleagues found that, on average, those individuals who carried the genotype associated with higher social anxiety were less likely to engage in prosocial behavior.
“Previous research has shown that the brain’s serotonin neurotransmitter system plays an important role in regulating emotions,” said study co-author Scott Stoltenberg, an associate professor at the University of Nebraska-Lincoln. “Our findings suggest that individual differences in social anxiety levels are influenced by this serotonin system gene and that these differences help to partially explain why some people are more likely than others to behave prosocially. Studies like this one show that biological factors are critical influences on how people interact with one another.”
Because prosocial behavior is linked to genetically based anxiety, Carlo suggests that helping nervous individuals cope with their social anxiety through targeted efforts, such as encouragement, support, counseling and medication, could help them engage in more prosocial behavior.
“Some forms of anxieties can be very debilitating for individuals,” Carlo said. “When people have severe levels of social anxiety, such as agoraphobia, which is the fear of public places and large crowds, they will avoid social situations altogether and miss the prosocial opportunities.”
Carlo said that it is difficult to distinguish how much of prosocial behavior is based on learned environmental behavior and how much is biologically based.
“The nature-versus-nurture debate is always interesting,” Carlo said. “However, I think that in our contemporary models of human behavior, we are beginning to understand the interplay between biology and the environment.”
Much of Carlo’s previous study on prosocial development has focused on how environmental influences, such as family relationships, influence prosocial behavior. This study brings researchers closer to understanding the effect that individuals’ biological makeup has on their behaviors, Carlo said.
A shot of anxiety and the world stinks
In evolutionary terms, smell is among the oldest of the senses. In animals ranging from invertebrates to humans, olfaction exerts a primal influence as the brain continuously and subconsciously processes the steady stream of scent molecules that waft under our noses.
And while odors — whether the aroma of stinky socks or the sweet smell of baking bread — are known to stir the emotions, how they exert their influence biologically on the emotional centers of the human brain, evoking passion or disgust, has been a black box.
Now, however, researchers using powerful new brain imaging technologies are peeling back some of the mystery, revealing how anxiety or stress can rewire the brain, linking centers of emotion and olfactory processing, to make typically benign smells malodorous.
Writing today (Sept. 24, 2013) in the Journal of Neuroscience, a team led by Wen Li, a professor of psychology at the UW-Madison Waisman Center, reports that the brains of human subjects experience anxiety induced by disturbing pictures and text of things like car crashes and war transform neutral odors to distasteful ones, fueling a feedback loop that could heighten distress and lead to clinical issues like anxiety and depression.
The finding is important because it may help scientists understand the dynamic nature of smell perception and the biology of anxiety as the brain rewires itself under stressful circumstances and reinforces negative sensations and feelings.
"After anxiety induction, neutral smells become clearly negative," explains Li, who conducted the study with UW-Madison colleagues Elizabeth Krusemark and Lucas Novak, and Darren Gitelman of Northwestern University’s Feinberg School of Medicine. "People experiencing an increase in anxiety show a decrease in the perceived pleasantness of odors. It becomes more negative as anxiety increases."
Using behavioral techniques and functional magnetic resonance imaging (fMRI), Li’s group looked at the brains of a dozen human subjects with induced anxiety as they processed known neutral odors.
Functional MRI is a technology that enables clinicians and researchers to observe the working brain in action. Before entering the MRI where screens cycle through a series of disturbing pictures and text, subjects were exposed to and rated a panel of neutral smells.
In the course of the experiment, the Wisconsin team observed that two distinct and typically independent circuits of the brain — one dedicated to olfactory processing, the other to emotion — become intimately intertwined under conditions of anxiety. Subsequent to anxiety induction and the imaging process, subjects were asked again to rate the panel of neutral smells, most assigning negative responses to smells they previously rated as neutral.
"In typical odor processing, it is usually just the olfactory system that gets activated," says Li. "But when a person becomes anxious, the emotional system becomes part of the olfactory processing stream."
Although those two systems of the brain are right next to each other, under normal circumstances there is limited crosstalk between the two. However, under conditions of induced anxiety, the Wisconsin team observed the emergence of a unified network cutting across the two systems.
The results may have clinical implications in the sense that it begins to uncover the biological mechanisms at play during periods of anxiety. “We encounter anxiety and as a result we experience the world more negatively. The environment smells bad in the context of anxiety. It can become a vicious cycle, making one more susceptible to a clinical state of anxiety as the effects accumulate. It can potentially lead to a higher level of emotional disturbances with rising ambient sensory stress.”
Size of personal space is affected by anxiety
The space surrounding the body (known by scientists as ‘peripersonal space’), which has previously been thought of as having a gradual boundary, has been given physical limits by new research into the relationship between anxiety and personal space.
New findings have allowed scientists to define the limit of the ‘peripersonal space’ surrounding the face as 20-40cm away. The study is published today in The Journal of Neuroscience.
As well as having numerical limits the specific distance was found to vary between individuals. Those with anxiety traits were found to have larger peripersonal space.
In an experiment, Dr Chiara Sambo and Dr Giandomenico Iannetti from UCL recorded the blink reflex - a defensive response to potentially dangerous stimuli at varying distances from subject’s face. They then compared the reflex data to the results of an anxiety test where subjects rated their levels of anxiety in various situations.
Those who scored highly on the anxiety test tended to react more strongly to stimuli 20cm from their face than subjects who got low scores on the anxiety test. Researchers classified those who reacted more strongly to further away stimuli as having a large ‘defensive peripersonal space’ (DPPS).
A larger DPPS means that those with high anxiety scores perceive threats as closer than non-anxious individuals when the stimulus is the same distance away. The research has led scientists to think that the brain controls the strength of defensive reflexes even though it cannot initiate them.
Dr Giandomenico Iannetti (UCL Neuroscience, Physiology and Pharmacology), lead author of the study, said: “This finding is the first objective measure of the size of the area surrounding the face that each individual considers at high-risk, and thus wants to protect through the most effective defensive motor responses.”
In the experiment, a group of 15 people aged 20 to 37 were chosen for study. Researchers applied an intense electrical stimulus to a specific nerve in the hand which causes the subject to blink. This is called the hand-blink reflex (HBR) which is not under conscious control of the brain.
This reflex was monitored with the subject holding their own hand at 4, 20, 40 and 60 cm away from the face. The magnitude of the reflex was used to determine how dangerous each stimulus was considered, and a larger response for stimuli further from the body indicated a larger DPPS.
Subjects also completed an anxiety test in which they self-scored their predicted level of anxiety in different situations. The results of this test were used to classify individuals as more or less anxious, and were compared to the data from the reflex experiment to determine if there was a link between the two tests.
Scientists hope that the findings can be used as a test to link defensive behaviours to levels of anxiety. This could be particularly useful determining risk assessment ability in those with jobs that encounter dangerous situations such as fire, police and military officers.
Brain circuit can tune anxiety
New findings may help neuroscientists pinpoint better targets for antianxiety treatments.
Anxiety disorders, which include posttraumatic stress disorder, social phobias and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as antianxiety drugs, are not always effective and have unwanted side effects.
To develop better treatments, a more specific understanding of the brain circuits that produce anxiety is necessary, says Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory.
“The targets that current antianxiety drugs are acting on are very nonspecific. We don’t actually know what the targets are for modulating anxiety-related behavior,” Tye says.
In a step toward uncovering better targets, Tye and her colleagues have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels. By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels.
Lead authors of the paper, which appears in the Aug. 21 issue of Neuron, are technical assistant Ada Felix-Ortiz and postdoc Anna Beyeler. Other authors are former research assistant Changwoo Seo, summer student Christopher Leppla and research scientist Craig Wildes.
Measuring anxiety
Both the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact.
To study those interactions, the researchers turned to optogenetics, which allows them to engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA); these neurons send long projections to cells of the ventral hippocampus.
The researchers tested the mice’s anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges.
When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when these mice had this pathway turned back on, they scampered back to the security of the edges.
Complex interactions
In a study published in 2011, Tye found that activating a different subset of neurons in the amygdala had the opposite effect on anxiety as the neurons studied in the new paper, suggesting that anxiety can be modulated by many different converging inputs.
“Neurons that look virtually indistinguishable from each other in a single region can project to different regions and these different projections can have totally opposite effects on anxiety,” Tye says. “Anxiety is such an important trait for survival, so it makes sense that you want some redundancy in the system. You want a couple of different avenues to modulate anxiety.”
The Neuron study contributes significantly to scientists’ understanding of the roles of the amygdala and hippocampus in anxiety and offers directions for seeking new drug targets, says Joshua Gordon, an associate professor of psychiatry at Columbia University.
“The study specifies a particular connection in the brain as being important for anxiety. One could imagine, then, identifying components of the machinery of that connection — synaptic proteins or ion channels, for example — that are particularly important for amygdala-hippocampal connectivity. If such specific components could be identified, they would be potential targets for novel antianxiety drugs,” says Gordon, who was not part of the research team.
In future studies, the MIT team plans to investigate the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety. Deciphering these circuits could be an important step toward finding better drugs to help treat anxiety.
Mood is Influenced by Immune Cells Called to the Brain in Response to Stress
New research shows that in a dynamic mind-body interaction during the interpretation of prolonged stress, cells from the immune system are recruited to the brain and promote symptoms of anxiety.
The findings, in a mouse model, offer a new explanation of how stress can lead to mood disorders and identify a subset of immune cells, called monocytes, that could be targeted by drugs for treatment of mood disorders.
The Ohio State University research also reveals new ways of thinking about the cellular mechanisms behind the effects of stress, identifying two-way communication from the central nervous system to the periphery – the rest of the body – and back to the central nervous system that ultimately influences behavior.
Unlike an infection, trauma or other problems that attract immune cells to the site of trouble in the body, this recruitment of monocytes that can promote inflammation doesn’t damage the brain’s tissue – but it does lead to symptoms of anxiety.
The research showed that the brain under prolonged stress sends signals out to the bone marrow, calling up monocytes. The cells travel to specific regions of the brain and generate inflammation that causes anxiety-like behavior.
In experiments conducted in mice, the research showed that repeated stress exposure caused the highest concentration of monocytes migrating to the brain. The cells surrounded blood vessels and penetrated brain tissue in several areas linked to fear and anxiety, including the prefrontal cortex, amygdala and hippocampus, and their presence led to anxiety-like behavior in the mice.
“In the absence of tissue damage, we have cells migrating to the brain in response to the region of the brain that is activated by the stressor,” said John Sheridan, senior author of the study, professor of oral biology and associate director of Ohio State’s Institute for Behavioral Medicine Research (IBMR).
“In this case, the cells are recruited to the brain by signals generated by the animal’s interpretation of social defeat as stressful.”
The research appears in the Aug. 21, 2013, issue of The Journal of Neuroscience.
Mice in this study were subjected to stress that might resemble a person’s response to persistent life stressors. In this model of stress, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours. This elicits a “fight or flight” response in the resident mice as they are repeatedly defeated. The experience of social defeat leads to submissive behaviors and the development of anxiety-like behavior.
Mice subjected to zero, one, three or six cycles of this social defeat were then tested for anxiety symptoms. The more cycles of social defeat, the higher the anxiety symptoms; mice took longer to enter an open space and opted for darkness rather than light when given the choice. Anxiety symptoms corresponded to higher levels of monocytes that had traveled to the animals’ brains from the blood.
Additional experiments showed that these cells did not originate in the brain, but traveled there from the bone marrow. In previous studies, this same research group showed that cells in the brain called microglia, the brain’s first line of immune defense, are activated by prolonged stress and are partly responsible for the signals that call up monocytes from the bone marrow.
“There are different moving parts from the central and peripheral components, and what’s novel is them coming together to influence behavior,” said Jonathan Godbout, a senior co-author of the paper and an associate professor of neuroscience at Ohio State.
Exactly what happens at this point in the brain remains unknown, but the research offers clues. The monocytes that travel to the brain don’t respond to natural anti-inflammatory steroids in the body and have characteristics signifying they are in a more inflammatory state. These results indicate that inflammatory gene expression occurs in the brain in response to the stressor.
“The monocytes are coming out of the bone marrow and they are not responsive to steroid regulation, so they overproduce proinflammatory signals when they’re stimulated. We think this is the key to the prolonged anxiety-like disorders that we see in these animals,” Sheridan said.
These findings do not apply to all forms of anxiety, the scientists noted, but they are a game-changer in research on stress-related mood disorders.
“Our data alter the idea of the neurobiology of mood disorders,” said Eric Wohleb, first author of the study and a predoctoral fellow in Ohio State’s Neuroscience Graduate Studies Program. “These findings indicate that a bidirectional system rather than traditional neurotransmitter pathways may regulate some forms of anxiety responses. We’re saying something outside the central nervous system – something from the immune system – is having a profound effect on behavior.”
(Source: newswise.com)