Li Jia, Li Dan, Yang Yongsheng, Xu Tiantian, Li Ping, He Defu
Laboratory of Toxicology, School of Ecological and Environmental Sciences, East China Normal University, Shanghai, People's Republic of China.
Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, Shanghai, People's Republic of China.
J Appl Toxicol. 2016 Jan;36(1):60-7. doi: 10.1002/jat.3144. Epub 2015 Apr 15.
Acrylamide can form in foods during the cooking process and cause multiple adverse effects. However, the neurotoxicity and mechanisms of acrylamide have not been fully elucidated. In Caenorhabditis elegans, we showed that 48 h exposure to 10-625 mg l(-1) acrylamide resulted in a significant decline in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, acrylamide exposure reduced crawling speeds and changed angles of body bending. It indicates that acrylamide induces locomotor defects, along with parkinsonian-like movement impairment, including bradykinesia and hypokinesia. Acrylamide also affected chemotaxis plasticity and reduced learning ability. Using transgenic nematodes, we found that acrylamide induced downexpression of P(dat-1) and led to the degeneration of dopaminergic neurons. Moreover, the enhanced expression of unc-54, encoding a subunit of α-synuclein was found. It illustrates that acrylamide is efficient in inducing crucial parkinsonian pathology, including dopaminergic damage and α-synuclein aggregation. These findings suggest the acrylamide-induced locomotor defects and neurotoxicity are associated with Parkinson's disease.
丙烯酰胺可在烹饪过程中于食物中形成，并引发多种不良影响。然而，丙烯酰胺的神经毒性及其机制尚未完全阐明。在秀丽隐杆线虫中，我们发现，暴露于10 - 625毫克/升的丙烯酰胺48小时会导致身体弯曲、头部摆动和咽部蠕动的运动频率显著下降。此外，丙烯酰胺暴露会降低爬行速度并改变身体弯曲角度。这表明丙烯酰胺会诱发运动缺陷，以及类似帕金森病的运动障碍，包括运动迟缓与运动功能减退。丙烯酰胺还会影响趋化性可塑性并降低学习能力。通过使用转基因线虫，我们发现丙烯酰胺会诱导P（dat - 1）的表达下调，并导致多巴胺能神经元退化。此外，还发现编码α - 突触核蛋白一个亚基的unc - 54表达增强。这说明丙烯酰胺能有效诱发关键的帕金森病病理变化，包括多巴胺能损伤和α - 突触核蛋白聚集。这些发现表明，丙烯酰胺诱发的运动缺陷和神经毒性与帕金森病有关。
