Stress regulators in the brain discovered

Scientists now understand better how stress affects the brain. New research reveals pioneering evidence for a new mechanism of stress adaptation. This may lead to a better understanding of why prolonged exposure to stress can lead to anxiety disorders and depression.

Some stressful event or stimuli will cause the release of corticotropin-releasing hormones (CRH) from neurons in the brain. As soon as the CRH-containing neurons run out of CRH, they are already receiving directions to make more. More and more CRH is creasted. This hormone controls the brain’s reaction to stress. The “fight or flight” response is one of those reactions as well as the more delayed responses associated with rationality. Regulation of CRH activity is critical for adaptation to stress. Multiple human psychiatric disorders are associated with abnormal regulation of CRH.

“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,” explained Dr. Gil Levkowitz, senior study author from the 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.”

The protein Orthopedia (Otp) modulated CRH and was required for stress adaptation. They showed they Otp regulates production of two different receptors on the neurons’ surface – the “on” and “off” buttons.

“The 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,” concluded Dr. Levkowitz.

Source: ScienceDaily, Neuron