The biological mechanisms behind stress-related psychiatric conditions, including major depressive disorder and post-traumatic stress disorder (PTSD), are poorly understood.
New research now details the interaction between proteins involved in controlling the body stress response and points to possible therapeutic targets when this response is twisted. The study, which was conducted by an international team led by researchers at McLean Hospital, appears in the journal Cell reports.
“A deregulated response to body stress can be detrimental to the brain and promote mood susceptibility and anxiety disorderssaid lead author Jakob Hartmann, Ph.D. Hartmann is an assistant neuroscientist at McLean’s Laboratory of Fear Neurobiology and a psychiatry instructor at Harvard Medical School.
“A key brain region involved in regulating the stress response is the hippocampus,” Hartmann said. “The idea for this study came to us when we observed interesting distinctions in the hippocampal localization of three important stress-regulating proteins.”
Researchers ’experiments on nonhuman tissues and postmortem brain tissue revealed how these proteins, the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and FK506-binding protein 51 (FKBP5) interact with each other.
Specifically, MRs, rather than GRs, control FKBP5 production under normal conditions. FKBP5 decreases the sensitivity of GRs to binding stress hormones during stressful situations. FKBP5 appears to fine-tune the stress response by acting as a mediator of MR: GR balance in the hippocampus.
“Our findings suggest that the therapeutic orientation of GR, MR, and FKBP5 may be complementary in the manipulation of central and peripheral stress regulation,” said lead author Kerry J. Ressler, MD, Ph.D. . Ressler is the scientific director of McLean Hospital, head of McLean’s Division of Depression and Anxiety Disorders, and a professor of psychiatry at Harvard Medical School.
“In addition, our data further underscore the important, but largely underappreciated, role of MRI signaling in Stress“The results of this study will open new directions for future research,” Ressler added.
Jakob Hartmann et al, Mineralocorticoid receptors dampen glucocorticoid receptor sensitivity to stress by regulation of FKBP5, Cell reports (2021). DOI: 10.1016 / j.celrep.2021.109185
Citation: New Study Finds Details of Body Response to Stress (2021, June 18) Retrieved June 18, 2021 at https://medicalxpress.com/news/2021-06-uncovers-body-response- stress.html
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