α-linolenic acid mitigates microglia-mediated neuroinflammation of schizophrenia in mice by suppressing the NF-κB/NLRP3 pathway via binding GPR120-β-arrestin 2.

Autor: Wang T; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: wangting950417@126.com., Liu S; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: 2561466083@qq.com., Shen W; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: 13139580422@163.com., Liu J; Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: 18222466512@163.com., Liu Y; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: liuyy18795171681@163.com., Li Y; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: 13995307059@163.com., Zhang F; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: 18309582195@163.com., Li T; Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: ltina1224@163.com., Zhang X; General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: zhangxiaoxuxh@163.com., Tian W; Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: 18995161584@163.com., Zhang J; Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: 18095420160@163.com., Ma J; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: 18195220598@163.com., Guo Y; General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: 3378069852@qq.com., Mi X; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: xiaomirly@163.com., Lin Y; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: linyuan893@126.com., Hu Q; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: huqikuan@163.com., Zhang X; College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: zxx1216@163.com., Liu J; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China; General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: liujuan@nxmu.edu.cn., Wang H; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China. Electronic address: wanghaograduate@126.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt A), pp. 113047. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1016/j.intimp.2024.113047
Abstrakt: Background: Schizophrenia (SCZ) is a heterogeneous psychiatric disorder that is poorly treated by current therapies. Emerging evidence indicates that SCZ is closely correlated with a persistent neuroinflammation. α-linolenic acid (ALA) is highly concentrated in the brain and represents a modulator of the immune system by decreasing the inflammatory response in chronic metabolic diseases. This study was first designed to investigate the potential role of dietary ALA on cognitive function and neuroinflammation in mice with SCZ.
Methods: In vivo, after 2 weeks of modeling, mice were treated with dietary ALA treatment for 6 weeks. In vitro, inflammation model was created using lipopolysaccharide as an inducer in BV2 microglial cells.
Results: Our results demonstrated that ALA alleviated cognitive impairment and enhanced synaptic plasticity in mice with SCZ. Moreover, ALA mitigated systematic and cerebral inflammation through elevating IL-10 and inhibiting IL-1β, IL-6, IL-18 and TNF-α. Furthermore, ALA notably inhibited microglia and pro-inflammatory monocytes, as well as microglial activation andpolarization. Mechanistically, ALA up-regulated the expressions of G protein coupled receptor (GPR) 120 and associated β-inhibitor protein 2 (β-arrestin2), accompanied by observable weakened levels of transforming growth factor-β activated kinase 1 (TAK1), NF-κB p65, cysteine proteinase-1 (caspase-1), pro-caspase-1, associated speck-like protein (ASC) and NLRP3. In vitro, ALA directly restrained the inflammation of microglia by decreasing the levels of pro-inflammatory factors and regulating microglial polarization via GPR120-NF-κB/NLRP3inflammasome signaling pathway, whereas AH7614 definitely eliminated this anti-inflammatory effect of ALA.
Conclusion: Dietary ALA ameliorates microglia-mediated neuroinflammation by suppressing the NF-κB/NLRP3 pathway via binding GPR120-β-arrestin2.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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