An on/off switch for stress


New research has shed some light on how the brain adapts to stress. There is pioneering evidence of a new mechanism of stress adaptation. This revelation may eventually lead to a better understanding of why prolonged stress can lead to anxiety disorders and depression.

Stressful episodes cause a release of corticotropin-releasing hormone (CRH) from neurons in the brain. This is followed by rapid changes in the CRH gene expression. As soon as CRH-containing hormones release all their CRH, they are given orders to create more. CRH is responsible for the “fight or flight” response therefore regulation of CRH for adaptation to stress is critical in development. Abnormal release of CRH is linked to multiple psychiatric disorders.

“Despite the wealth of information regarding the physiological role of CRH in mediating the response to stress, the molecular mechanisms that regulate expression of the CRH gene, and thereby CRH synthesis, have remained largely elusive,” explains Dr. Gil Levkowitz, Weizmann Institute of Science in Israel. “In our study, we used mouse and zebrafish model systems to identify a novel intracellular signaling pathway that controls stress-induced CRH gene expression.”

Dr. Levkowitz discovered that the protein Orthopedia (Otp) modulates CRH gene expression in parts of the brain associated with stress adaptation. They found that Otp regulates production of two different receptors on the neurons’ surface. The receptor serve as on/off switches.

“This regulation of the CRH gene is critical for neuronal adaptation to stress. Failure to activate or terminate the CRH response can lead to chronic over- or under-activation of stress-related brain circuits, leading to pathological conditions,” said Dr. Levkowitz.

Source: Cell Press, MedicalNewsToday


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