TY - JOUR
T1 - The involvement of oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation in acrylamide-induced neurotoxicity in C57/BL6 mice
AU - Zhao, Mengyao
AU - Deng, Linlin
AU - Lu, Xiaoxuan
AU - Fan, Liqiang
AU - Zhu, Yang
AU - Zhao, Liming
PY - 2022/6
Y1 - 2022/6
N2 - 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 α-synuclein (α-syn), further inhibiting cholinergic and dopaminergic neuronal function. Additionally, ACR treatment caused an inflammatory response via nuclear factor-kappa B (NF-κB) 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-1β (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 pathway strategy for investigating the risk posed by ACR. Graphical abstract: The hypothetical mechanism of ACR-induced neurotoxicity in vivo.[Figure not available: see fulltext.]
AB - 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 α-synuclein (α-syn), further inhibiting cholinergic and dopaminergic neuronal function. Additionally, ACR treatment caused an inflammatory response via nuclear factor-kappa B (NF-κB) 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-1β (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 pathway strategy for investigating the risk posed by ACR. Graphical abstract: The hypothetical mechanism of ACR-induced neurotoxicity in vivo.[Figure not available: see fulltext.]
KW - Acrylamide
KW - Neuroinflammation
KW - Neurotoxicity
KW - Neurotransmission impairment
KW - NLRP3 inflammasome
KW - Oxidative stress
U2 - 10.1007/s11356-021-18146-2
DO - 10.1007/s11356-021-18146-2
M3 - Article
AN - SCOPUS:85123928761
SN - 0944-1344
VL - 29
SP - 41151
EP - 41167
JO - Environmental Science and Pollution Research
JF - Environmental Science and Pollution Research
IS - 27
ER -