文献类型：期刊文献

英文题名：The involvement of oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation in acrylamide-induced neurotoxicity in C57/BL6 mice

作者：Zhao, Mengyao[1];Deng, Linlin[1];Lu, Xiaoxuan[1];Fan, Liqiang[1];Zhu, Yang[2];Zhao, Liming[1]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Wageningen Univ & Res, Bioproc Engn Grp, POB 16, NL-6700 AA Wageningen, Netherlands

年份：2022

卷号：29

期号：27

起止页码：41151

外文期刊名：ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH

收录：;EI(收录号：20242616383841);WOS:【SCI-EXPANDED(收录号:WOS:000749248200026)】；

基金：This project was financially supported by the National Natural Science Foundation for Young Scientists of China (No. 31801668), the Fundamental Research Funds for the Central Universities (grant number 222201814036, 22221818014), the Shanghai PuJiang Program (18J1401900), the 111 Project (B18022), and the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, ECUST (ZDXM2019).

语种：英文

外文关键词：Acrylamide; Oxidative stress; Neurotoxicity; Neurotransmission impairment; Neuroinflammation; NLRP3 inflammasome

摘要：Acrylamide (ACR) is a typical environmental contaminant, presenting potential health hazards that have been attracting increasing attention. Its neurotoxicity is known to cause significant damage to health. However, the mechanisms of ACR-induced neurotoxicity require further clarification. This study uses a mouse model to explore how ACR-induced oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation mutually contribute to neurotoxicity. A distinct increase in the cellular reactive oxygen species (ROS) levels, malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG) content and a significant decrease in the glutathione (GSH) content after ACR exposure were indicative of oxidative stress. Moreover, ACR caused neurological defects associated with gait abnormality and neuronal loss while suppressing the acetylcholine (ACh) and dopamine (DA) levels and increasing the protein expression of alpha-synuclein (alpha-syn), further inhibiting cholinergic and dopaminergic neuronal function. Additionally, ACR treatment caused an inflammatory response via nuclear factor-kappa B (NF-kappa B) activation and increased the protein expression of NOD-like receptor protein-3 (NLRP3), consequently activating the NLRP3 inflammasome constituents, including cysteinyl aspartate specific proteinase 1 (Caspase-1), apoptosis-associated speck-like protein containing CARD (ASC), N domain gasdermin D (N-GSDMD), interleukin-1 beta (IL-1 beta), and IL-18. The results revealed the underlying molecular mechanism of ACR-induced neurotoxicity via oxidative stress, neurotransmission impairment, and neuroinflammation-related signal cascade. This information will further improve the development of an alternative pathway strategy for investigating the risk posed by ACR.