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Neurosteroids: of the nervous system, by the nervous system, for the nervous system.
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1997
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Cerebral OrganoidGlucocorticoidPeripheral NervesPeripheral Nervous SystemNeuroendocrine MechanismNeurologyNeurochemistrySteroid MetabolismHealth SciencesHormonal ReceptorNeurohormonesSciatic NerveNeuropharmacologyProgesterone 3Nervous SystemEndocrinologyPharmacologyNeuroanatomyPhysiologyNeuroscienceCentral Nervous SystemCentral Nervous System BiologyMedicine
Neurosteroids are synthesized in the nervous system, mainly by glial cells from cholesterol or imported precursors, and act as allosteric modulators of neurotransmitter receptors such as GABAA, NMDA, and sigma receptors, with concentrations that vary with environmental and behavioral conditions. The study aims to investigate how abnormal neurosteroid concentrations or metabolism could be targeted to treat functional and trophic disturbances of the nervous system. Physiological evidence shows hippocampal pregnenolone supports memory in aging rats, while Schwann cell–derived progesterone promotes myelin repair after sciatic nerve injury and supports dorsal root ganglia neurite growth.
Neurosteroids are synthesized in the central and peripheral nervous system, particularly but not exclusively in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources. They include 3 beta-hydroxy-delta 5-compounds, such as pregnenolone (PREG) and dehydroepiandrosterone (DHEA), their sulfates, and reduced metabolites such as the tetrahydroderivative of progesterone 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha,5 alpha-THPROG). These compounds can act as allosteric modulators of neurotransmitter receptors, such as GABAA, NMDA, and sigma receptors. Progesterone (PROG) is also a neurosteroid, and a progesterone receptor (PROG-R) has been identified in peripheral and central glial cells. At different places in the brain, neurosteroid concentrations vary according to environmental and behavioral circumstances, such as stress, sex recognition, or aggressiveness. A physiological function of neurosteroids in the central nervous system is strongly suggested by the role of hippocampal PREGS with respect to memory, observed in aging rats. In the peripheral nervous system, a role for PROG synthesized in Schwann cells has been demonstrated in the repair of myelin after cryolesion of the sciatic nerve in vivo and in cultures of dorsal root ganglia neurites. It may be important to study the effect of abnormal neurosteroid concentrations/metabolism with a view to the possible treatment of functional and trophic disturbances of the nervous system.