in stress effects on the brain
Acute and chronic stress can have devastating effects on the brain, and Yale School of Medicine researchers have pinpointed
one receptor that plays a key role in that harmful cycle, it was reported
Jan. 15 in the Proceedings of the National Academy of Sciences. — By Jacqueline Weaver
T H I S
IN MEMORIAM
“This could provide new targets for the development of antidepressant medications,” says
Ronald Duman, professor of psychiatry and pharmacology and senior author of the
study.
Duman says uncontrollable stress is a major contributing factor for neuropsychiatric
disorders such as major depression and post-traumatic stress disorders, which
have been linked to cellular changes in the hippocampus. The hippocampus is
a part of the brain that is particularly susceptible to stress.
But little is known about the underlying mechanisms that block the growth of
new neurons, which are needed for antidepressants to be effective in treating
depression and anxiety.
The researchers discovered in this mouse study that when activated, the receptor
for IL-1ß prevents the brain from creating new neurons. It also decreased
the animals’ preference for a sweetened solution, a response that mirrors
the inability to feel pleasure that people with depression experience.
IL-1ß is a cytokine — or signaling compound — that promotes
inflammation. Previous animal studies showed that exposure to stress increases
IL-1ß in several brain areas, including the hippocampus. It also has
been demonstrated that administering IL-1ß produces several stress-like
effects in the hypothalamus, pituitary and adrenal systems as well as the hippocampus.
The team blocked the effects of IL-1ß with an inhibitor, resulting in
a blockade of cell cycle arrest.
“This is the first study to show how IL-1ß — when activated
by acute and chronic stress — arrests the cell cycle,” says Duman.
Ja Wook Koo of Yale is lead author of the paper.
The research was supported by TU.S. Public Health Service grants, a Veterans
Administration National Center Grant for Post-Traumatic Stress Disorder, and
the Connecticut Mental Health Center.
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