Wang Lei, Fu HuanHuan, Liu Bin, Liu XiaoYan, Chen WeiWei, Yu XiaoDan
Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Ministry of Education Shanghai Key Laboratory of Children's Environmental Health, Shanghai 200127, China, Shanghai, 200127, China.
Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai, 201102, China.
J Biochem Mol Toxicol. 2017 Dec;31(12). doi: 10.1002/jbt.21969. Epub 2017 Dec 4.
Overexposure to manganese (Mn) is associated with neurological disorders in children. Evidence indicated that N-methyl-d-aspartate (NMDA) receptor signaling pathway was critical for neurobehavioral function. However, whether NMDA receptor signaling pathway contributes to Mn-induced neurotoxicity remains unknown. In this study, newborn Sprague-Dawley rats were randomly assigned to four groups exposed to 0, 10, 20, and 30 mg/kg of Mn by intraperitoneal injection (n = 10/group: five males and five females). After 3 weeks of Mn exposure, messenger RNA (mRNA) and protein expression of NMDA receptor subunits (NR1, NR2A, and NR2B), cAMP-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by real-time quantitative RT-PCR and Western blot. In Mn-exposed rats, decreased mRNA and protein expression of NR1, NR2A, and NR2B, CREB, and BDNF was observed. The results imply that downregulated NMDA receptor signaling pathway may be of vital importance in the neuropathological process of Mn-induced neurotoxicity.
儿童过度暴露于锰（Mn）与神经功能障碍有关。有证据表明，N-甲基-D-天冬氨酸（NMDA）受体信号通路对神经行为功能至关重要。然而，NMDA受体信号通路是否参与锰诱导的神经毒性作用尚不清楚。在本研究中，将新生Sprague-Dawley大鼠随机分为四组，通过腹腔注射给予0、10、20和30 mg/kg的锰（每组n = 10：五只雄性和五只雌性）。锰暴露3周后，通过实时定量RT-PCR和蛋白质印迹法检测海马中NMDA受体亚基（NR1、NR2A和NR2B）、环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）的信使核糖核酸（mRNA）和蛋白质表达。在锰暴露的大鼠中，观察到NR1、NR2A和NR2B、CREB以及BDNF的mRNA和蛋白质表达降低。结果表明，NMDA受体信号通路下调可能在锰诱导的神经毒性神经病理过程中至关重要。
