Effects of Testosterone Treatment on Synaptic Plasticity and Behavior in Senescence Accelerated Mice

Learning and memory are known to be influenced by circulating sex steroidal hormones and these behavioral processes are diminished in aging. Thus, the aim of this study was to examine the mechanism underlying testosterone-induced effects on cognitive performance in the senescence accelerated mouse P8 (SAMP8) model. Treatment with testosterone (T) as evidenced by the Morris water maze test produced a significantly shorter escape latency and reduced path length to reach the platform compared to the control (C). No significant differences were noted in mean swim speed among all groups. During the probe trials, the T group spent a significantly greater percent of time in the target quadrant and improved the number of platform crossings. Flutamide (F), an antiandrogen, significantly inhibited the effects of T on behavioral and memory performances indicators. Following Nissl staining, the number of intact pyramidal cells was markedly elevated in the treated mice, and this effect was blocked by F. Immunohistochemistry and Western blot analysis showed that the expression levels of NMDAR1, SYN, and p-CREC/CREB protein levels were significantly increased in the T group, while F inhibited the T-mediated effects. Western blot analysis showed that there were no significant differences in the expression levels of SYN, p-CREC/CREB, and NMDAR1 between C, F, and F + T groups. Reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that the mRNA expression levels of NMDAR1 and SYN were significantly increased in T-administered mice, while F inhibited the T-mediated effects. Data suggest that the T-mediated increase in SYN expression levels resulted in improvement in behavioral performances and learning, which may involve stimulation of central nervous system androgen receptors (AR).