Biological and Genetic Resources Utilization Division, National Institute of Biological Resources, Hwangyeong-ro 42, Seo-gu, Incheon 404-708, Republic of Korea.
Department of Medical Biomaterials Engineering, College of Biomedical Science, Kangwon National University, Hyoja-2 Dong, Chuncheon 200-701, Republic of Korea.
Evid Based Complement Alternat Med. 2014;2014:869831. doi: 10.1155/2014/869831. Epub 2014 Dec 24.
The aim of the present study was to evaluate the effect of ENS on cognitive impairment induced by scopolamine and its potential neuroprotective effect against glutamate-induced cytotoxicity in HT22 cell and to investigate the underlying mechanisms. ENS (3, 10, 30, and 100 mg/kg), scopolamine (1 mg/kg), and donepezil (1 mg/kg) were administered to mice during a test period. Scopolamine impaired memory and learning in a water maze test and a passive avoidance test. The neuroprotective effect of ENS (10 and 100 μg/mL) was investigated on glutamate-induced cell death in HT22 cells by MTT assay. We investigated acetylcholinesterase inhibition in hippocampus and antioxidant activity, ROS levels, and Ca(2+) influx in HT22 cells to elucidate the potential mechanisms of ENS. We found that ENS significantly ameliorated scopolamine-induced memory impairment and inhibited AChE activity in hippocampus. In vitro, ENS showed potent neuroprotective effects against glutamate-induced neurotoxicity in the HT22 cell. In addition, ENS induced a decrease in ROS production and intercellular Ca(2+) accumulation and showed DPPH radical and H2O2 scavenging activity. In conclusion, ENS showed both a memory improving effect and a neuroprotective effect. Our results indicate that ENS may be of use in the treatment and prevention of neurodegenerative disorders.
本研究旨在评估电神经刺激（ENS）对东莨菪碱诱导的认知障碍的影响及其对 HT22 细胞中谷氨酸诱导的细胞毒性的潜在神经保护作用，并探讨其潜在机制。在测试期间，ENS（3、10、30 和 100mg/kg）、东莨菪碱（1mg/kg）和多奈哌齐（1mg/kg）被给予小鼠。东莨菪碱在水迷宫测试和被动回避测试中损害记忆和学习。通过 MTT 测定法研究了 ENS（10 和 100μg/mL）对 HT22 细胞中谷氨酸诱导的细胞死亡的神经保护作用。我们研究了海马中的乙酰胆碱酯酶抑制作用以及抗氧化活性、ROS 水平和 HT22 细胞中的 Ca（2+）内流，以阐明 ENS 的潜在机制。我们发现 ENS 显著改善了东莨菪碱诱导的记忆障碍，并抑制了海马中的 AChE 活性。在体外，ENS 对 HT22 细胞中谷氨酸诱导的神经毒性表现出强大的神经保护作用。此外，ENS 诱导 ROS 产生和细胞内 Ca（2+）积累减少，并表现出 DPPH 自由基和 H2O2 清除活性。总之，ENS 表现出改善记忆和神经保护作用。我们的结果表明，ENS 可能可用于治疗和预防神经退行性疾病。
