Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer's disease  

作　　者：Xu-Sheng Yan Zhan-Jun Yang Jian-Xin Jia Wei Song Xin Fang Zhi-Ping Cai Dong-Sheng Huo He Wang 

机构地区：[1]Department of Human Anatomy, Baotou Medical College [2]School of Health Sciences, University of Newcastle,Newcastle, Australia

出　　处：《Neural Regeneration Research》2019年第4期649-657,共9页中国神经再生研究（英文版）

基　　金：supported by the Natural Science Foundation of Inner Mongolia Autonomous Region of China,No.2017LH0301(to JXJ),2016MS08108(to ZJY);Science and Technology Planning Project of Inner Mongolia Autonomous Region of China,No.201602069(to ZJY);PhD Scientific Research Fund of Baotou Medical College of China,No.BSJJ201606(to JXJ);"Dengfeng Project" Scientific Research Fund of Baotou Medical College of China,No.BYJJ-DF 201703(to JXJ)

摘　　要：Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.

关 键 词：nerve REGENERATION Alzheimer’s disease TESTOSTERONE cognitive dysfunction synaptic plasticity free radicals MORRIS water maze androgen receptor FLUTAMIDE POSTSYNAPTIC density protein 95 amyloid beta 1–42 NEURODEGENERATIVE change neural REGENERATION 

分 类 号：R459.1[医药卫生—治疗学] R749[医药卫生—临床医学]