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Canna~Fangled Abstracts

CB2R Activation Regulates TFEB-Mediated Autophagy and Affects Lipid Metabolism and Inflammation of Astrocytes in POCD

By March 22, 2022April 9th, 2022No Comments

. 2022 Mar 22;13:836494.

doi: 10.3389/fimmu.2022.836494. eCollection 2022.

Lieliang Zhang 1 2, Xifeng Wang 3, Wen Yu 1 2, Jun Ying 1 2, Pu Fang 4, Qingcui Zheng 1 2, Xiaojin Feng 1 2, Jialing Hu 1 2, Fan Xiao 1 2, Shoulin Chen 1 2, Gen Wei 1 2, Yue Lin 1 2, Xing Liu 1 2, Danying Yang 1 2, Yang Fang 1 2, Guohai Xu 1 2, Fuzhou Hua 1 2
Affiliations 

Abstract

Evidence suggests that the accumulation of lipid drots (LDs) accelerates damage to mitochondria and increases the release of inflammatory factors. These have been implicated as a mechanism underlying neurodegenerative diseases or tumors and aging-related diseases such as postoperative cognitive dysfunction (POCD), nevertheless, accumulation of lipid droplets has not been extensively studied in the central nervous system (CNS). Here, we found that after surgery, there was activation of astrocytes and lipid accumulation in the hippocampus. However, cannabinoid receptor type II (CB2R) activation significantly reduced lipid accumulation in astrocytes and change the expression of genes related to lipid metabolism. CB2R reduces the release of the inflammatory factors interleukin-1 beta (IL-1β) and interleukin 6 (IL-6) in peripheral serum and simultaneously improves cognitive ability in mice with POCD. Further research on mechanisms indicates that CB2R activation promotes the nuclear entry of the bHLH-leucine zipper transcription factor, the transcription factor EB (TFEB), and which is a master transcription factor of the autophagy-lysosomal pathway, also reduces TFEB-S211 phosphorylation. When CB2R promotes TFEB into the nucleus, TFEB binds at two sites within promoter region of PGC1α, promoting PGC1α transcription and accelerating downstream lipid metabolism. The aforementioned process leads to autophagy activation and decreases cellular lipid content. This study uncovers a new mechanism allowing CB2R to regulate lipid metabolism and inflammation in POCD.

Keywords: astrocytes, autophagy, cannabinoid type 2 receptor, inflammation, lipid accumulation, mitochondrial damage, postoperative cognitive dysfunction

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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