Non-neuronal cells in the nervous system: sources and targets of neuroactive steroids

Non-neuronal cells synthethize and metabolize steroid hormones and produce local neuroactive steroids that exert neuromodulatory and neurotrophic actions under physiological and pathological conditions. In the central nervous system, the steroids produced by non-neuronal cells, such as pregnenolone, dehydroepiandrosterone (DHEA), testosterone, estradiol, progesterone and other steroid metabolites, regulate synaptic function, affect anxiety, cognition, sleep and behavior and exert neuroprotective and reparative roles. In the peripheral nervous system, progesterone and progesterone derivatives producted by Schwann cells, promote myelin formation, the remyelination and regeneration of injured nerves. non-neuronal cells are also targets for steroids and mediate or partecipate in many of the actions of these substances in the nervouis system. These include: (i) the regulation of blood-brain barrier and cerebrovascular permeability by actions of steroid on endothelial cells; (ii) the regulation of synaptogenesis, synaptic plasticity, neuritic growth and neuroendocrine secretion by actions of steroids on astroglia and (iii) the regulation of neuronal survival and regeneration by actions of steroids on microglia, astroglia and Schwann cells.