Abstract
Since the first observations on the existence of “neurosteroids” in the 1980s, our understanding of the importance of these endogenous steroids in the control of the central and peripheral nervous system (PNS) has increased progressively. Although most of the observations were made in neuronal cells, equally important are the effects that neurosteroids exert on glial cells. Among the different classes of neurosteroids acting on glial cells, the progesterone 5α-3α metabolite, allopregnanolone, displays a particular mechanism of action involving primarily the modulation of classic GABA receptors. In this review, we focus our attention on allopregnanolone because its effects on the physiology of glial cells of the central and PNS are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues.
Highlights
The first observations on the existence of “nervous steroids” appeared in the early 1980s, introducing the novel concept that some hormonal steroids may be synthesized de novo in the nervous system. Baulieu (1997) coined the term “neurosteroids” in order to define such molecules
We focus our attention on allopregnanolone because its effects on the physiology of glial cells of the central and peripheral nervous system (PNS) are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues
We have recently demonstrated in vitro a cross-correlation between the γ-aminobutyric acid (GABA)-A and B receptors in Schwann cells (SC) (Magnaghi, 2007), and some of these effects are discussed below
Summary
The first observations on the existence of “nervous steroids” appeared in the early 1980s, introducing the novel concept that some hormonal steroids may be synthesized de novo in the nervous system. Baulieu (1997) coined the term “neurosteroids” in order to define such molecules. Support neuron metabolism and survival, they can uptake and produce neurotransmitters and they are able to synthesize neurosteroids (Celotti et al, 1992; Melcangi et al, 2001b). The simultaneous presence of neurons and type 1 astrocyte cultures stimulates the 5α-R activity (Melcangi et al, 2001c), indicating a possible interaction of these cells in the metabolism of neurosteroids. Gago et al (2001) showed that the formation of the 5αreduced metabolite of P, dehydroprogesterone (DHP), is fivefold higher in fully differentiated oligodendrocytes compared to oligodendrocyte progenitor cells.
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