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

Abstract

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).

Influence of Testosterone Depletion on Neurotrophin-4 in Hippocampal Synaptic Plasticity and Its Effects on Learning and Memory

“…Thus, testosterone’s neuro-supportive potentials play an influential role in exhibiting synaptic plasticity [62]. Furthermore, the reduced dendritic spines in the ORX indicate a feature of abnormal excitatory synapses and reduced LTP [63]. These observations correlated with hampered spatial learning on a hippocampus-dependent version of RAM in ORX rats.…”

Sex-Dependent Differences in Physical Exercise-Mediated Cognitive Recovery Following Middle Cerebral Artery Occlusion in Aged Rats

“…In contrast to females, in male rats, reproductive aging is not well defined, and occurs much later in lifespan resulting in decreased fertility. Since the current study used RS female and age matched male rats, the effects of estrogen on cognition might be weaned off while those of testosterone (Bimonte-Nelson et al, 2003; Jian-xin et al, 2015) may persist and reflect on improved post-stroke cognition in exercised male rats. In middle-aged rats, similar to men, exercise training increases testosterone, sex-hormone binding globulin, and endothelial nitric oxide (e-NOS) (Zmuda et al, 1996; Seo et al, 2018).…”

Impact of Testosterone on Alzheimer’s Disease

“…Furthermore, T prevented vascular and neuronal aging by increasing eNOS activity and stimulating SIRT1 expression [ 14 ]. The behavioral performance and learning was associated with an increased SYN expression levels [ 15 ]. Dihydrotestosterone (DHT) appeared to be more effective treatment to reduce the onset of dementia [ 16 ].…”