Acrylamide (ACR), a potential neurotoxin, is present in diet and drinking water. Dietary exposure contributes to cognitive impairment, but relevant mechanism information is limited. Neuroinflammation plays important roles in neurodegenerative disorders. This study aimed to explore whether chronic acrylamide exposure induced neuronal lesions, microglial activation, NLRP3 inflammasome-mediated neuroinflammation and cognitive impairment. For this purpose, 36 Sprague-Dawley (SD) rats were randomly divided into three groups (n = 12/group) and maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. Chronic exposure to ACR caused gait abnormality and cognitive dysfunction, which was associated with neuronal lesions, decrease in synapse associated proteins including synapsin I (SYN1), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), neurogenesis suppression as shown by reduced brain derived neurotrophic factor (BDNF) and doublecortin (DCX) in the hippocampus and frontal cortex. ACR stimulated glial proliferation and microglial activation by increasing GFAP⁺, Iba-1⁺, Iba-1⁺CD68⁺ positive cells. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3, caspase-1 and increased pro-IL-1β and IL-1β. ACR elevated the protein P62 to suppress NLPR3 inflammasome cleavage. Inflammatory cytokines including TNF-α, IL-6 and Cox-2 were also significantly increased after NF-κB pathway activation, which aggravated neuronal lesions and caused memory deficits. This work helped to propose the possible mechanism of chronic exposure of ACR-induced neurotoxicity.

饮食和饮用水中存在丙烯酰胺（ACR），这是一种潜在的神经毒素。饮食接触会导致认知障碍，但相关的机制信息有限。神经炎症在神经退行性疾病中起重要作用。这项研究旨在探讨慢性丙烯酰胺暴露是否会引起神经元病变，小胶质细胞激活，NLRP3炎性小体介导的神经发炎和认知障碍。为此，将36只Sprague-Dawley（SD）大鼠随机分为三组（n = 12 /组），并保持在经过处理的饮用水中，提供0、0.5或5 mg / kg /天的ACR剂量，持续12个月。长期暴露于ACR会导致步态异常和认知功能障碍，这与神经元病变有关，包括突触素I（SYN1），突触素（SYP）和突触后密度蛋白95（PSD95）在内的突触相关蛋白减少，神经减少被大脑减少所显示海马和额叶皮层中的神经营养因子（BDNF）和双皮质素（DCX）。ACR通过增加GFAP ⁺，Iba-1 ⁺，Iba-1 ⁺ CD68 ⁺刺激神经胶质增生和小胶质细胞活化阳性细胞。ACR明显上调了NLRP3炎性小体成分NLRP3，caspase-1的蛋白水平，并增加了前IL-1β和IL-1β的表达。ACR升高了蛋白P62，以抑制NLPR3炎性体裂解。NF-κB途径激活后，包括TNF-α，IL-6和Cox-2在内的炎性细胞因子也显着增加，这加剧了神经元病变并引起记忆缺陷。这项工作有助于提出ACR诱导的神经毒性慢性暴露的可能机制。