The Involvement of Oxidative Stress, Neuronal Lesions, Neurotransmission Impairment, and Neuroinflammation in Acrylamide-Induced Neurotoxicity

Abstract Acrylamide (ACR) is a typically contaminate during environmental industry and poses 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 explores how ACR-induced oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation mutually contribute to neurotoxicity using a mouse model. According to the results, oxidative stress was indicated by the presence of a distinct increase in cellular reactive oxygen species levels, malondialdehyde, and 8-hydroxy-2-deoxyguanosine content, as well as a significant decrease in the glutathione content after ACR exposure. Moreover, ACR caused neurological defects associated with gait abnormality and neuronal loss while suppressing the levels of acetylcholine and dopamine and increasing the protein expression of α-syn, further inhibiting cholinergic and dopaminergic neuronal function. Additionally, ACR treatment caused an inflammation response via NF-κB activation and increased the protein expression of NLRP3. Consequently, ACR activated the NLRP3 inflammasome constituents, including Caspase-1, ASC, N-GSDMD, IL-1β, 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 outcome pathway strategy for investigating the risk posed by ACR.