Effects of androgens on cognitive function in castration male mice

Acta Universitatis Medicinalis Anhui     font:big middle small

Fund programs: Natural Science Research Project of Anhui Educational Committee(No. 2022AH051141)

Authors:Zhang Yaqi¹, Hui Cancan², Ren Fang³, Xu Min¹, Jiang Zilong⁴, Deng Datong¹,⁵

Keywords:androgen; testosterone propionate; castration; TRT; behavioral tests; brain-derived neurotrophic factor; cognition

DOI:10.19405/j.cnki.issn1000-1492.2026.03.010

〔Abstract〕 Objective To establish a castrated male mouse model and to preliminarily investigate the effects of testosterone 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 assessed 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 significantly reduced escape latency on days 4 and 5 (P0.05), while the number of platform crossings and the time spent in the target quadrant significantly increased (P0.05). Passive avoidance test: the number of passive avoidance errors significantly decreased in sham operation group and testosterone propionate (1.0 mg/kg)-treated group (P0.05), and the passive avoidance latency was significantly prolonged in sham-operated group and testosterone propionate-treated groups (0.5, 1.0 mg/kg) (P0.05). Serum testosterone and serum BDNF assays: serum testosterone levels and serum BDNF concentrations significantly increased in sham operation group and testosterone propionate-treated groups (0.5, 1.0 mg/kg) (P0.01). HE staining: compared with sham operation group, neuronal 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 pyramidal 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 modulation of hippocampal BDNF signaling pathways.