Testosterone Influence on Microtubule-Associated Proteins and Spine Density in Hippocampus: Implications on Learning and Memory

Abstract

The thorny protrusions or spines increase the neuronal surface area, facilitate synaptic interconnections among neurons, and play an essential role in the hippocampus. Increasing evidence suggests that testosterone, the gonadal hormone plays an important role in neurogenesis and synaptic plasticity. The role of testosterone on microtubule-associated proteins on dendritic neurite stability in the hippocampus and its impact on learning disability not elucidated. Adult male Wistar albino rats were randomly selected for the control, castrated, castrated + testosterone, and control + testosterone groups. Bilateral orchidectomy was done, and the testosterone propionate was administered during the entire trial period, i.e., 14d. The learning assessments were done using working/reference memory versions of the 8-arm radial maze and hippocampal tissues processed for histological and protein expressions. There were reduced expressions of microtubule-associated protein2 (MAP2), postsynaptic density protein 95 (PSD95), and androgen receptor (AR) and increased expression of pTau in the castrated group. Conversely, the expression of MAP2, PSD95 and AR were increased, and the pTau expression was reduced in the hippocampus of the castrated rat administrated with testosterone. Androgen-depleted rat showed impaired synaptic plasticity in hippocampus associated with contracted microtubule dynamics. Accompanying learning disability, with an increased number of reference memory errors (RME) and working memory errors (WME) in castrated rats. Observations suggest that androgen regulates expression of neural tissue-specific MAPs and play a vital role in hippocampus synaptic plasticity, and a similar mechanism may underlie neurological disorders in aging and hypogonadal men

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