TY - JOUR
T1 - GABA receptor-mediated effects in the peripheral nervous system
T2 - A cross-interaction with neuroactive steroids
AU - Magnaghi, Valerio
AU - Ballabio, Marinella
AU - Consoli, Antonio
AU - Lambert, Jeremy J.
AU - Roglio, Ilaria
AU - Melcangi, Roberto C.
PY - 2006/1
Y1 - 2006/1
N2 - γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult mammalian central nervous system (CNS), exerts its action via an interaction with specific receptors (e.g., GABAA and GABA B). These receptors are expressed not only in neurons but also on glial cells of the CNS, which might represent a target for the allosteric action of neuroactive steroids. Herein, we have demonstrated first that in the peripheral nervous system (PNS), the sciatic nerve and myelin-producing Schwann cells express both GABAA and GABAB receptors. Specific ligands, muscimol and baclofen, respectively, control Schwann-cell proliferation and expression of some specific myelin proteins (i.e., glycoprotein P0 and peripheral myelin protein 22 [PMP22]). Moreover, the progesterone (P) metabolite allopregnanolone, acting via the GABAA receptor, can influence PMP22 synthesis. In addition, we demonstrate that P, dihydroprogesterone, and allopregnanolone influence the expression of GABAB subunits in Schwann cells. The results suggest, at least in the myelinating cells of the PNS, a cross-interaction within the GABAergic receptor system, via GABA A and GABAB receptors and neuroactive steroids.
AB - γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult mammalian central nervous system (CNS), exerts its action via an interaction with specific receptors (e.g., GABAA and GABA B). These receptors are expressed not only in neurons but also on glial cells of the CNS, which might represent a target for the allosteric action of neuroactive steroids. Herein, we have demonstrated first that in the peripheral nervous system (PNS), the sciatic nerve and myelin-producing Schwann cells express both GABAA and GABAB receptors. Specific ligands, muscimol and baclofen, respectively, control Schwann-cell proliferation and expression of some specific myelin proteins (i.e., glycoprotein P0 and peripheral myelin protein 22 [PMP22]). Moreover, the progesterone (P) metabolite allopregnanolone, acting via the GABAA receptor, can influence PMP22 synthesis. In addition, we demonstrate that P, dihydroprogesterone, and allopregnanolone influence the expression of GABAB subunits in Schwann cells. The results suggest, at least in the myelinating cells of the PNS, a cross-interaction within the GABAergic receptor system, via GABA A and GABAB receptors and neuroactive steroids.
KW - Allopregnanolone
KW - GABA receptor
KW - Myelin
KW - Peripheral nervous system
KW - Progesterone
KW - Schwann cell
U2 - 10.1385/JMN:28:1:89
DO - 10.1385/JMN:28:1:89
M3 - Review article
C2 - 16632878
AN - SCOPUS:33646866348
VL - 28
SP - 89
EP - 102
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 1
ER -