Testosterone and brain aging

Testosterone is an essential hormone to maintain brain health and function. It also exerts a specific activity on the peripheral nervous system, maintaining skeletal muscle activity. The brain has a wide distribution of androgen receptors (AR) in the cortical area, hippocampus, hypothalamus, telencephalon, and amygdala. AR is also in the brainstem and spinal cord areas associated with sensory functions and in Purkinje cells of the cerebellar cortex. ARs were found on axons and dendrites, evidencing extranuclear activity. Testosterone regulates neuronal growth, differentiation, survival, or death through both genomic and nongenomic signaling pathways. Testosterone is metabolized in other hormones: in DHT acting on the hippocampus and 17β-estradiol, which explicitly affects dendritic arborization in females and males. Furthermore, testosterone stimulates oligodendrocytes and myelin formation, while estrogens stimulate mitochondrial activity, anti-inflammatory effect, and astrocytes protection. Testosterone improves the survival of human neurons and astrocytes, acting directly on the mitochondrial membrane and inhibiting the reactive oxygen species. Furthermore, it exerts a protective effect on brain function, preventing Alzheimer’s disease, reducing the formation of amyloid β(Aβ) peptides in cortical neurons, and neurotoxicity. Furthermore, testosterone is an effective therapy to restore hippocampal function and related pathology, increasing adult neurogenesis within the dentate gyrus region of the hippocampus through an androgen-dependent pathway. Testosterone stimulates myelin regeneration, representing the primary therapeutic goal in demyelinating diseases. There is evidence that it can be effective in various neurodegenerative diseases, such as Parkinson’, SLA, and multiple sclerosis (MS). In this review, the effect of testosterone on neurons, demyelinating diseases, muscle strength loss, mood, and depression have been investigated.