Supraphysiological androgen administration does not exert any additive benefits on hippocampal plasticity-related markers and behavior in previously untrained male mice

This study examined the effects of resistance training (RT) and supraphysiological nandrolone decanoate (ND) administration on hippocampal neurogenesis, neurotrophic signaling, and behavior. Forty 3-month-old male C57BL/6 J mice were randomized to RT or sedentary (SED) conditions. Each group was further divided into sham (S) or ND (38 mg·kg−1·wk.−1) treatment groups. All interventions lasted 7 wk. Adult hippocampal neurogenesis was quantified in the dentate gyrus using BrdU+/NeuN+ immunolabeling. Hippocampal expression of brain-derived neurotrophic factor (BDNF), androgen receptor (AR), estrogen receptor-β (ER-β), insulin-like growth factor-1 (IGF-1), and irisin was assessed by western blot analyses. No significant exercise × treatment interactions were observed for any of the behavior measures. When collapsed across treatments, RT exhibited a greater number of open-arm entries (p = 0.006) and reduced average latency times (p = 0.002) than SED. ND administration did not alter behavioral outcomes. RT (p = 0.001) and ND (p = 0.032) each independently increased hippocampal BrdU+/NeuN+ cell numbers, with no additive effects. AR expression for SED-S was significantly lower (p's < 0.05) than all other groups and IGF-1 expression for RT-S was significantly greater (p's < 0.05) than all other groups. Main effects revealed that RT and ND resulted in significant elevations in AR, ER-β and BDNF expressions. In conclusion, RT enhanced hippocampal plasticity and behavioral performance, whereas supraphysiological ND administration produced distinct molecular changes without conferring additive behavioral or neuroplastic benefit.