[The role of neurosteroids in the central nervous system function].
Neurosteroids--important modulators of the central nervous system activity--have been biochemically and functionally well characterized in recent years. Inhibitory neurosteroids are positive allosteric modulators of GABAA receptors which show anxiolytic and anticonvulsant properties, whereas negative modulators of GABAA receptors facilitate memory processes and at high doses show proconvulsant activity. Allopregnanolone is the most potent inhibitory neurosteroid, and the reduced metabolites of deoxycorticosterone and androgens have similar though weaker action. Pregnenolone, dehydroepiandrosterone and their sulfate derivatives, belong to stimulating neurosteroids, that besides the inhibitory effect on GABAA receptors enhance activity of glutamatergic NMDA receptors and sigma1 receptors which leads to an increase in acetylcholine release, in consequence, strengthening cognitive processes. Neurosteroids seem to be also involved in neuronal cell regeneration, regulation of hypothalamic-pituitary-adrenal axis activity and in the mechanism of drug dependence and depression. In contrast to well-documented beneficial effects of some neurosteroids on animal brain function, scarce clinical data do not allow to draw final conclusions about potential usefulness of these compounds in diagnosis or treatment of neurological and psychiatric disorders.
Basta-Kaim
Agnieszka
A
Zakład Neuroendokrynologii Doświadczalnej, Instytut Farmakologii Polskiej Akademii Nauk, Kraków.
Leśkiewicz
Monika
M
Budziszewska
Bogusława
B
Lasoń
Władysław
W
D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology*; D003900:Desoxycorticosterone / Q000502:physiology*; D006801:Humans; D011280:Pregnanolone / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D003900:Desoxycorticosterone; D011280:Pregnanolone