February 12, 2014
Chronic Stress Generates Long-Term Changes In The Brain Which Could Lead To Mental Illness
April Flowers for redOrbit.com - Your Universe Online
Chronic stress generates long-term changes in the brain, according to a new study from the University of California, Berkeley. These changes may explain why people suffering from chronic stress are prone to mental problems such as anxiety and mood disorders.The findings, published in the journal Molecular Psychiatry, might lead to new therapies to reduce the risk of developing mental illness after stressful events.
Robert Sanders of UC Berkeley reports doctors have known for a while that people with stress-related illnesses, such as post-traumatic stress disorder (PTSD), have abnormalities in the brain. These abnormalities include differences in the amount of gray matter versus white matter. Grey matter is mainly formed of cells — neurons, which store and process information, and support cells called glia. White matter, in contrast, consists mainly of axons, which create a network of fibers that interconnect neurons, and gets its name from the white, fatty myelin sheath that surrounds the axons and speeds the flow of electrical signals from cell to cell.
Researchers are only now starting to unravel the mystery of how chronic stress creates these long-lasting changes in brain structure.
Daniela Kaufer, UC Berkeley associate professor of integrative biology, and a team of colleagues performed a series of experiments, discovering that chronic stress generates more myelin-producing cells and fewer neurons than normal. The delicate balance and timing of communication within the brain is disrupted by this resulting excess of myelin — and thus white matter — in some areas of the brain.
“We studied only one part of the brain, the hippocampus, but our findings could provide insight into how white matter is changing in conditions such as schizophrenia, autism, depression, suicide, ADHD and PTSD,” Kaufer told Sanders.
Memory and emotions are regulated by the hippocampus, which also plays a role in various emotional disorders.
Kaufer's findings, for example, suggest a mechanism that might explain some changes in brain connectivity in individuals with PTSD. Kaufer said that it is easy to imagine that PTSD patients could develop a stronger connectivity between the hippocampus and the amygdala — which is the seat of the brain's fight of flight response — and a lower than average connectivity between the hippocampus and the prefrontal cortex — which moderates our responses to stimuli.
“You can imagine that if your amygdala and hippocampus are better connected, that could mean that your fear responses are much quicker, which is something you see in stress survivors,” she said. “On the other hand, if your connections are not so good to the prefrontal cortex, your ability to shut down responses is impaired. So, when you are in a stressful situation, the inhibitory pathways from the prefrontal cortex telling you not to get stressed don’t work as well as the amygdala shouting to the hippocampus, ‘This is terrible!’ You have a much bigger response than you should.”
Kaufer is involved in a study to test her hypothesis in PTSD patients, as well as continuing to study brain changes in rodents subjected to chronic stress or adverse environments early in life.
Kaufer's lab conducts research on the molecular and cellular effects of acute and chronic stress. This study focused on neural stem cells in the hippocampus of the brains of adult rats. Previously, these stem cells were thought to mature only into neurons or a type of glial cell called an astrocyte. Kaufer's team found, however, that chronic stress also made stem cells in the hippocampus mature into another type of glial cell called an oligodendrocyte, which produces myelin that sheaths nerves cells.
The team demonstrated their findings in rats and cultured rat brain cells, suggesting a key role for oligodendrocytes in long-term and perhaps permanent changes in the brain that could set the stage for later mental problems. These cells also help form synapses — areas where one cell communicates with another - and help control the growth pathway of axons, which make those synapse connections.
Kaufer said that the fact that chronic stress also decreases the number of stem cells that mature into neurons could suggest an explanation for how chronic stress also affects learning and memory.
Kaufer's research team is continuing their investigations with experiments designed to determine how stress in infancy affects the brain’s white matter, and whether chronic early-life stress decreases resilience later in life. They are also examining the effects of therapies, ranging from exercise to antidepressant drugs, that reduce the impact of stress and stress hormones.
Image 2 (below): Myelin is stained blue in this cross section of a rat hippocampus. Myelin, which speeds electrical signals flowing through axons, is produced by oligodendrocytes, which increase in number as a result of chronic stress. New oligodendrocytes are shown in yellow. Credit: Aaron Friedman and Daniela Kaufer