Department of Histology and Embryology, Institute of Neuroscience , Wenzhou Medical University , Wenzhou , Zhejiang 325035 , P.R. China.
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology , Hallym University , Chuncheon 24252 , South Korea.
ACS Chem Neurosci. 2018 Aug 15;9(8):2016-2024. doi: 10.1021/acschemneuro.7b00278. Epub 2017 Sep 27.
Melatonin is known to improve cognitive deficits, and its functions have been studied in various disease models, including Alzheimer's disease. In this study, we investigated effects of melatonin on cognition and the cholinergic system of the septum and hippocampus in a mouse model of scopolamine-induced amnesia. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally to mice for 2 and 4 weeks. The Morris water maze and passive avoidance tests revealed that both treatments of scopolamine significantly impaired spatial learning and memory; however, 2- and 4-week melatonin treatments significantly improved spatial learning and memory. In addition, scopolamine treatments significantly decreased protein levels and immunoreactivities of choline acetyltransferase (ChAT), high-affinity choline transporter (CHT), vesicular acetylcholine transporter (VAChT), and muscarinic acetylcholine receptor M1 (M1R) in the septum and hippocampus. However, the treatments with melatonin resulted in increased ChAT-, CHT-, VAChT-, and M1R-immunoreactivities and their protein levels in the septum and hippocampus. Our results demonstrate that melatonin treatment is effective in improving the cognitive deficits via restoration of the cholinergic system in the septum and hippocampus of a mouse model of scopolamine-induced amnesia.
褪黑素已知可改善认知缺陷，其功能已在各种疾病模型中进行了研究，包括阿尔茨海默病。在这项研究中，我们研究了褪黑素对东莨菪碱诱导的健忘症小鼠模型中隔核和海马认知功能和胆碱能系统的影响。腹腔内给予东莨菪碱（1mg/kg）和褪黑素（10mg/kg），连续 2 和 4 周。Morris 水迷宫和被动回避测试表明，两种东莨菪碱处理均显著损害空间学习和记忆；然而，2 周和 4 周的褪黑素处理显著改善了空间学习和记忆。此外，东莨菪碱处理显著降低了隔核和海马中的胆碱乙酰转移酶（ChAT）、高亲和力胆碱转运蛋白（CHT）、囊泡乙酰胆碱转运蛋白（VAChT）和毒蕈碱乙酰胆碱受体 M1（M1R）的蛋白水平和免疫反应性。然而，褪黑素处理导致隔核和海马中的 ChAT、CHT、VAChT 和 M1R 免疫反应性及其蛋白水平增加。我们的结果表明，褪黑素治疗通过恢复东莨菪碱诱导的健忘症小鼠模型中隔核和海马中的胆碱能系统，有效改善了认知缺陷。
