GABA Receptor-Mediated Effects in the Peripheral Nervous System: A Cross-Interac

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J Mol Neurosci. 2006 Jan;28(1):89-102.

GABA Receptor-Mediated Effects in the Peripheral Nervous System: A

Cross-Interaction With Neuroactive Steroids.

Magnaghi V, Ballabio M, Consoli A, Lambert JJ, Roglio I, Melcangi RC.

Department of Endocrinology and Center of Excellence on

Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy.

ã-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 GABAB).

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 GABAA and

GABAB receptors and neuroactive steroids.