Neurosteroids, a new function in the brain:: neurotrophicity, memory, ageing...

Some steroids named neurosteroids, can be synthesized in the central and peripheral nervous system by neurons and glial cells. The study of their synthesis, metabolism, mechanisms of action and effects represents an expanding area of research and important progress has been made over the past few years. Although the synthesis of neurosteroids in the brain and in peripheral nerves is now when established its regulation has not been explored very much. A few recent studies show that the expression and the activity of enzymes involved in neurosteroid synthesis are regulated by cellular interactions, but the molecules which are involved remain to he identified (as for instance a neuronal factor inducing the synthesis of progesterone in Schwann cells). Research is now turning towards the functions of neurosteroids. Their mechanisms of action involve nuclear receptors, membrane receptors (particularly those affecting the function of neurotransmitters), and a recently discovered direct activity on microtubule-associated protein and tubulin polymerisation. Several recent studies have described psychopharmacological effects of neurosteroids, in particular on memory, anxiety and sleep as well as their role in regeneration. Thus, pregnenolone stimulates polymerisation of neuronal microtubules, pregnenolone sulfate has promnesic effects and progesterone promotes the formation of new myelin sheaths. Neurosteroid and analogues may therefore become useful to treat diseases and lesions of the nervous system.