Steroid synthesis and metabolism in the nervous system: Trophic and protective effects

Steroids influence the activity and plasticity of neurons and glial cells d uring early development, and they continue to exert trophic and protective effects in the adult nervous system. Steroids are produced by the gonads an d adrenal glands and reach the brain, the spinal cord and the peripheral ne rves via the bloodstream. However, some of them, named "neurosteroids", can also be synthesized within the nervous system. They include pregnenolone, progesterone, dehydroepiandrosterone and their reduced metabolites and sulf ate esters. Little is known concerning the regulation of steroid synthesis in the nervous system, which involves interactions between different cell t ypes For example, the synthesis of progesterone by Schwann cells in periphe ral nerves is regulated by a diffusible neuronal signal. Neuro trophic and neuroprotective effects of steroids have been documented both in cell cultu re and in vivo. PROG plays an important role in the neurological recovery f rom traumatic injury of the brain and spinal cord by mechanisms involving p rotection from excitotoxic cell death, lipid peroxydation and the induction of specific enzymes. After transection of the rat spinal cord, PROG increa ses the number of nitric oxide synthase expressing astrocytes immediately a bove and below the lesion. PROG also plays an important role in the formati on of new myelin sheaths. This has been shown in the regenerating mouse sci atic nerve after lesion and in cocultures of sensory neurons and Schwann ce lls. PROG promotes myelination by activating the expression of genes coding for myelin proteins. The modulation of neurostransmitter receptors, in par ticular the type A gamma -aminobutyric acid, the N-methyl-D-aspartate and t he sigma 1 receptors, is involved in the psychopharmacological effects of s teroids and allows to explain their anticonvulsant, anxiolytic, antidepress ive and sedative effects as well as their influence on memory. Pregnenolone sulfate has been shown to reverse age-related deficits in spatial memory p erformance and to have protective effects on memory in different models of amnesia.