雄激素对去势雄性小鼠认知功能的影响OA

Objective To establish a castrated male mouse model and to preliminarily investigate the effects of tes-tosterone replacement therapy(TRT)on behavior,serum indices,and histopathological changes in castrated mice,as well as to explore the role of androgens in cognitive function.Methods Forty 6-month-old male C57/BL6J mice were randomly divided into sham operation group,castration group,testosterone propionate(0.5,1.0 mg/kg)treated group,with 10 mice in each group.Following castration and subcutaneous administration of testosterone propionate at different doses(0.5 and 1.0 mg/kg)for TRT,learning and memory abilities were as-sessed using the Morris water maze(MWM)test and the passive avoidance test.Serum testosterone and serum brain-derived neurotrophic factor(BDNF)levels were measured by ELISA,and histopathological changes in the hippocampus were examined using hematoxylin-eosin(HE)staining.Results Routine observations:there were no statistically significant differences in body weight among groups at any time point.MWM test:compared with castration group,sham operation group and testosterone propionate-treated groups(0.5,1.0 mg/kg)showed sig-nificantly reduced escape latency on days 4 and 5(P<0.05),while the number of platform crossings and the time spent in the target quadrant significantly increased(P<0.05).Passive avoidance test:the number of passive avoid-ance errors significantly decreased in sham operation group and testosterone propionate(1.0 mg/kg)-treated group(P<0.05),and the passive avoidance latency was significantly prolonged in sham-operated group and testosterone propionate-treated groups(0.5,1.0 mg/kg)(P<0.05).Serum testosterone and serum BDNF assays:serum tes-tosterone levels and serum BDNF concentrations significantly increased in sham operation group and testosterone propionate-treated groups(0.5,1.0 mg/kg)(P<0.01).HE staining:compared with sham operation group,neu-ronal density in all hippocampal subregions was slightly reduced in castration group;in the testosterone propionate(0.5 mg/kg)-treated group,neuronal arrangement in the CA1 and CA3 regions was improved and apoptotic cells were reduced compared with castration group;in testosterone propionate(1.0 mg/kg)-treated group,the pyrami-dal cell layer in the CA3 region was more compactly arranged,with fewer apoptotic cells than in castration group.Conclusion TRT improves learning and memory performance in castration male mice,potentially through modu-lation of hippocampal BDNF signaling pathways.