Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, PR China.
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon, 24252, Republic of Korea.
Chem Biol Interact. 2018 Apr 1;285:8-13. doi: 10.1016/j.cbi.2018.02.023. Epub 2018 Feb 21.
Animal models of scopolamine-induced amnesia are widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases such as Alzheimer's disease (AD). Previous studies have identified that melatonin improves cognitive dysfunction in animal models. In this study, using a mouse model of scopolamine-induced amnesia, we assessed spatial and short-term memory functions for 4 weeks, investigated the expression of myelin-basic protein (MBP) in the dentate gyrus, and examined whether melatonin and scopolamine cotreatment could keep cognitive function and MBP expression. In addition, to study functions of melatonin for keeping cognitive function and MBP expression, we examined expressions of brain-derived neurotrophic factor (BDNF) and tropomycin receptor kinase B (TrkB) in the mouse dentate gyrus. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally treated for 2 and 4 weeks. Two and 4 weeks after scopolamine treatment, mice showed significant cognitive impairment; however, melatonin and scopolamine cotreatment recovered cognitive impairment. Two and 4 weeks of scopolamine treatment, the density of MBP immunoreactive myelinated nerve fibers was significantly decreased in the dentate gyrus; however, scopolamine and melatonin cotreatment significantly increased the scopolamine-induced reduction of MBP expression in the dentate gyrus. Furthermore, the cotreatment of scopolamine and melatonin significantly increased the scopolamine-induced decrease of BDNF and TrKB immunoreactivity in the dentate gyrus. Taken together, our results indicate that melatonin treatment exerts anti-amnesic effect and restores the scopolamine-induced reduction of MBP expression through increasing BDNF and TrkB expressions in the mouse dentate gyrus.
东莨菪碱诱导的遗忘症动物模型被广泛用于研究神经退行性疾病（如阿尔茨海默病）认知障碍的潜在机制和治疗方法。先前的研究已经确定褪黑素可以改善动物模型的认知功能障碍。在这项研究中，我们使用东莨菪碱诱导的遗忘症小鼠模型，评估了 4 周的空间和短期记忆功能，研究了齿状回髓鞘碱性蛋白（MBP）的表达，并检查了褪黑素和东莨菪碱联合治疗是否可以保持认知功能和 MBP 表达。此外，为了研究褪黑素保持认知功能和 MBP 表达的功能，我们检查了小鼠齿状回中脑源性神经营养因子（BDNF）和 Tropomyosin 受体激酶 B（TrkB）的表达。腹腔内给予东莨菪碱（1mg/kg）和褪黑素（10mg/kg）2 周和 4 周。东莨菪碱处理 2 周和 4 周后，小鼠表现出明显的认知障碍；然而，褪黑素和东莨菪碱联合治疗恢复了认知障碍。2 周和 4 周的东莨菪碱处理，齿状回中 MBP 免疫反应性髓鞘神经纤维的密度明显降低；然而，褪黑素和东莨菪碱联合治疗显著增加了 MBP 表达的减少。此外，东莨菪碱和褪黑素的联合治疗显著增加了 BDNF 和 TrkB 免疫反应性在齿状回中的减少。总之，我们的结果表明，褪黑素治疗通过增加 BDNF 和 TrkB 在小鼠齿状回中的表达，发挥抗遗忘作用，并恢复东莨菪碱诱导的 MBP 表达减少。
