Protective effects of testosterone on cognitive dysfunction in Alzheimer's disease model rats induced by oligomeric beta amyloid peptide 1-42.
Cognitive dysfunction is known to be influenced by circulating sex steroidal hormones. The aim of this study was to examine the protective effect and possible protective mechanism of testosterone (T) on cognitive performance in male rats induced by intrahippocampal injections of beta amyloid 1-42 oligomers (Aβ1-42). Treatment with T as evidenced by the Morris water maze (MWM) test significantly shortened escape latency and reduced path length to reach the platform compared to the control (C). During probe trials, the T group displayed a significantly greater percent of time in the target quadrant and improved the number of platform crossings compared with C, flutamide (F), an antiandrogen, and a combined F and T group. Flutamide markedly inhibited the influence of T on cognitive performance. Following Nissl staining, the number of intact pyramidal cells was significantly elevated in the T group, and the effect of T was blocked by F. Immunohistochemisty and Western blot analysis showed that the protein expression level of Aβ 1-42 was markedly decreased and expression levels of synaptophysin (SYN) significantly increased with T, while F inhibited all T-mediated effects. Our data suggest that the influence of T on cognitive performance was mediated via androgen receptors (AR) to remove beta amyloid, which leads to enhanced synaptic plasticity.
a Department of Human Anatomy, Baotou Medical College, Baotou , Inner Mongolia , China.
Dong-Sheng
DS
Huo
b The First Affiliated Hospital of Baotou Medical College, Baotou , Inner Mongolia , China.
Jian-Fang
JF
Sun
a Department of Human Anatomy, Baotou Medical College, Baotou , Inner Mongolia , China.
Baifeng
B
Zhang
a Department of Human Anatomy, Baotou Medical College, Baotou , Inner Mongolia , China.
Xu-Sheng
XS
Yan
c School of Health Sciences , University of Newcastle , Newcastle , Australia.
He
H
Wang
a Department of Human Anatomy, Baotou Medical College, Baotou , Inner Mongolia , China.
Jian-Xin
JX
Jia
a Department of Human Anatomy, Baotou Medical College, Baotou , Inner Mongolia , China.
Zhan-Jun
ZJ
Yang
D000544:Alzheimer Disease / Q000150:complications; D016229:Amyloid beta-Peptides; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D005485:Flutamide / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments; D011897:Random Allocation; D051381:Rats; D016708:Synaptophysin / Q000494:pharmacology / Q000627:therapeutic use; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D000726:Androgen Antagonists; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D016708:Synaptophysin; C075222:amyloid beta-protein (1-42); D013739:Testosterone; D005485:Flutamide