Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer's disease
Xu-Sheng Yan
Zhan-Jun Yang
Jian-Xin Jia
Wei Song
Xin Fang
Zhi-Ping Cai
Dong-Sheng Huo
He Wang
摘要：Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxida-tive 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 hippocam-pal 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 en-hancing synaptic plasticity.
机标关键词：
资助基金：This study was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region of China, (No. 2017LH0301)the Science and Technology Planning Project of Inner Mongolia Autonomous Region of China, (No. 201602069)the PhD Scientific Research Fund of Baotou Medical College of China, (No. BSJJ201606)the "Dengfeng Project" Scientific Re-search Fund of Baotou Medical College of China, (No. BYJJ-DF 201703)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 649-657 )
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