Termination of acute stress response by the endocannabinoid system is regulated through lysine ‐specific demethylase 1‐mediated transcriptional repression of 2‐AG hydrolases ABHD6 and MAGL

Environmental stress engages physiological responses primed by synaptic activation. In the nucleus direct psychosocial stress effects induce a program of neuroplasticity ‐related gene expression instrumental to memory consolidation of the negative experience. On the behavioral point of view, stress response directly elicits anxiety arousal and increased vigilance. A slower homeostatic response to stress entails nuclear, synaptic, and behavioral adaptations instrum ental to stress response termination. We show that direct targets of LSD1 transcriptional repression at the nuclear level are 2‐AG degrading enzymes ABHD6 and MAGL. In response to stress their expression is reduced helping to maintain active 2‐AG concentrations via LSD1‐mediated mechanism. AbstractAcute environmental stress rarely implies long ‐lasting neurophysiological and behavioral alterations. On the contrary, chronic stress exerts a potent toxic effect at the glutamatergic synapse whose altered physiology has been recognized as a core trait of neuropsychiatric disorders. The endocannabinoid system (ECS) plays an important role in the homeostatic response to acute stress. In particular, stress induces synthesis of endocannabinoid (eCB) 2‐arachidonyl glycerol (2‐AG). 2‐AG stimulates presynaptic cannabinoid 1 (CB1) receptor contributing to stress response termination through inhibition of glutamate release, restraining th ereafter anxiety arousal. We employ mouse models of stress response coupled ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research