Aging, testosterone, and neuroplasticity: friend or foe?

Neuroplasticity or neural plasticity implicates the adaptive potential of the brain in response to extrinsic and intrinsic stimuli. The concept has been utilized in different contexts such as injury and neurological disease. Neuroplasticity mechanisms have been classified into neuroregenerative and function-restoring processes. In the context of injury, neuroplasticity has been defined in three post-injury epochs. Testosterone plays a key yet double-edged role in the regulation of several neuroplasticity alterations. Research has shown that testosterone levels are affected by numerous factors such as age, stress, surgical procedures on gonads, and pharmacological treatments. There is an ongoing debate for testosterone replacement therapy (TRT) in aging men; however, TRT is more useful in young individuals with testosterone deficit and more specific subgroups with cognitive dysfunction. Therefore, it is important to pay early attention to testosterone profile and precisely uncover its harms and benefits. In the present review, we discuss the influence of environmental factors, aging, and gender on testosterone-associated alterations in neuroplasticity, as well as the two-sided actions of testosterone in the nervous system. Finally, we provide practical insights for further study of pharmacological treatments for hormonal disorders focusing on restoring neuroplasticity.