Longaretti_2020_J.Neurochem__e15000

Reference

Title : Termination of acute stress response by the endocannabinoid system is regulated through LSD1-mediated transcriptional repression of 2-AG hydrolases ABHD6 and MAGL - Longaretti_2020_J.Neurochem__e15000
Author(s) : Longaretti A , Forastieri C , Gabaglio M , Rubino T , Battaglioli E , Rusconi F
Ref : Journal of Neurochemistry , :e15000 , 2020
Abstract :

Acute 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 thereafter anxiety arousal. We employ mouse models of stress response coupled to gene expression analyses, unravelling that in response to acute psychosocial stress in the mouse hippocampus, ECS-mediated synaptic modulation is enhanced via transcriptional repression of two enzymes involved in 2-AG degradation: alpha/beta-Hydrolase Domain containing 6 (ABHD6) and Monoacylglycerol Lipase (MAGL). Such a process is orchestrated by the epigenetic corepressor LSD1 who directly interacts with promoter regulatory regions of Abhd6 and Magl. Remarkably, negative transcriptional control of Abhd6 and Magl is lost in the hippocampus upon chronic psychosocial stress, possibly contributing to trauma-induced drift of synapse physiology toward uncontrolled glutamate transmission. We previously showed that in mice Lysine Specific Demethylase 1 (LSD1) increases its hippocampal expression in response to psychosocial stress preventing excessive consolidation of anxiety-related plasticity. With this work we unravel a nodal epigenetic modulation of eCB turn over, shedding new light on the molecular substrate of converging stress-terminating effects displayed by ECS and LSD1.

PubMedSearch : Longaretti_2020_J.Neurochem__e15000
PubMedID: 32141088
Gene_locus related to this paper: human-ABHD6 , human-MGLL , mouse-ABHD6 , mouse-MGLL

Related information

Gene_locus human-ABHD6    human-MGLL    mouse-ABHD6    mouse-MGLL

Citations formats

Longaretti A, Forastieri C, Gabaglio M, Rubino T, Battaglioli E, Rusconi F (2020)
Termination of acute stress response by the endocannabinoid system is regulated through LSD1-mediated transcriptional repression of 2-AG hydrolases ABHD6 and MAGL
Journal of Neurochemistry :e15000

Longaretti A, Forastieri C, Gabaglio M, Rubino T, Battaglioli E, Rusconi F (2020)
Journal of Neurochemistry :e15000