Trpv4 regulates Nlrp3 inflammasome via SIRT1/PGC-1 α pathway in a cuprizone-induced mouse model of demyelination.

Trpv4 regulates Nlrp3 inflammasome via SIRT1/PGC-1α pathway in a cuprizone-induced mouse model of demyelination.
Exp Neurol. 2020 Dec 30;:113593
Authors: Liu Y, Fan H, Li X, JingLiu, Qu X, Wu X, Liu M, Liu Z, Yao R
Abstract
Increasing evidence has demonstrated that the Nod-like receptor pyrin domain containing 3 (Nlrp3) inflammasome overactivated during demyelinating disorders. It has been implicated that transient receptor potential type 4 (Trpv4) is regarded as a polymodal ionotropic receptor that plays an important role in a multitude of pathological conditions, including inflammation. The aim of this study was to investigate whether the Trpv4 channel regulates Nlrp3 inflammasome in the corpus callosum of mice with demyelination. Our results showed that CPZ treatment significantly increased the expression of Trpv4, activated Nlrp3 inflammasome, reduced peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and decreased mitochondrial function. siRNA-mediated Nlrp3 knockdown inhibited glial activation and alleviated demyelination. Whereas knockdown of Trpv4 by siRNA markedly ameliorated Nlrp3 inflammasome activation and restored mitochondrial function as well as reducing the level of reactive oxygen species (ROS). Meanwhile, glial activation, demyelination and behavioral impairment induced by CPZ were also alleviated by siRNA-mediated Trpv4 knockdown. Furthermore, immunoprecipitation and use of a lysine acetyla...

Source: Experimental Neurology - December 30, 2020 Category: Neurology Authors: Liu Y, Fan H, Li X, JingLiu, Qu X, Wu X, Liu M, Liu Z, Yao R Tags: Exp Neurol Source Type: research