Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China; Department of Clinical Laboratory, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, PR China.
Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China.
Toxicol Appl Pharmacol. 2022 Sep 15;451:116190. doi: 10.1016/j.taap.2022.116190. Epub 2022 Jul 30.
Acrylamide (ACR) as a by-product of Maillard reaction is widely present in food. Although ACR is known to exhibit neurotoxicity, most studies about ACR neurotoxicity are currently short-term high-dose providing limited reference value for human exposure. The present study aims to determine the effects of chronic ACR exposure on dopaminergic neurons in rat nigra and the potential mechanism from the perspective of NLRP3 inflammasome-mediated neuroinflammation. The SD rats were maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. ACR exposure caused motor dysfunction in rats, which was associated with dopaminergic neuron loss, α-Synuclein (α-Syn) accumulation and decreased brain-derived neurotrophic factor (BDNF) in nigra. ACR activated microglia by increasing Iba-1, Iba-1CD68 positive cells and the percentage of ameboid-shaped ones in rat nigra. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3 and caspase-1 and inflammatory cytokine IL-1β. ACR chronic exposure increased the risk of Parkinson's disease (PD) like dopaminergic neuron depletion in nigra potentially through NLRP3 inflammasome-mediated neuroinflammtion.
丙烯酰胺（ACR）作为美拉德反应的副产物广泛存在于食品中。虽然已知丙烯酰胺具有神经毒性，但目前大多数关于丙烯酰胺神经毒性的研究都是短期高剂量的，对人类暴露的参考价值有限。本研究旨在从 NLRP3 炎性小体介导的神经炎症角度，确定慢性丙烯酰胺暴露对大鼠黑质多巴胺能神经元的影响及其潜在机制。SD 大鼠饮用含 0、0.5 或 5mg/kg/天丙烯酰胺的处理水 12 个月。丙烯酰胺暴露导致大鼠运动功能障碍，与黑质多巴胺能神经元丢失、α-突触核蛋白（α-Syn）积累和脑源性神经营养因子（BDNF）减少有关。丙烯酰胺通过增加大鼠黑质中 Iba-1、Iba-1CD68 阳性细胞和阿米巴样细胞的百分比，激活小胶质细胞。丙烯酰胺显著上调 NLRP3 炎性小体成分 NLRP3 和半胱天冬酶-1 以及炎症细胞因子 IL-1β的蛋白水平。慢性丙烯酰胺暴露增加了类似于帕金森病（PD）的黑质多巴胺能神经元缺失的风险，可能是通过 NLRP3 炎性小体介导的神经炎症。
