- Title
- Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer's disease
- Creator
- Yan, Xu-Sheng; Yang, Zhan-Jun; Jia, Jian-Xin; Song, Wei; Fang, Xin; Cai, Zhi-Ping; Huo, Dong-Sheng; Wang, He
- Relation
- Neural Regeneration Research Vol. 14, Issue 4, p. 649-657
- Publisher Link
- http://dx.doi.org/10.4103/1673-5374.245477
- Publisher
- Wolters Kluwer
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- nerve regeneration; Alzheimer's disease; amyloid beta 1-42; neurodegenerative change; neural regeneration; testosterone; cognitive dysfunction; synaptic plasticity; free radicals; Morris water maze; androgen receptor; flutamide; postsynaptic density protein 95
- Identifier
- http://hdl.handle.net/1959.13/1454999
- Identifier
- uon:45031
- Identifier
- ISSN:1673-5374
- Rights
- This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-Non-Commercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. (https://creativecommons.org/licenses/by-nc-sa/4.0/).
- Language
- eng
- Full Text
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