GABA-A and GABA-B receptors participate in the axon-Schwann cell interactions

The g-aminobutyrric acid (GABA) is the major inhibitory neurotransmitter responsible of neuron-to-neuron communication and also of neuron-to-glia interactions in the nervous system. In fact, different mechanisms involving the GABA receptors (i.e. GABA-AA and GABA-B receptors) seem to play pivotal roles during the development and differentiation of glial precursor cells. In the rat peripheral nervous system (PNS), both the rat sciatic nerve and the Schwann cells express the GABA-A and the GABA-B receptor isoforms, which are proved to be functionally active. A physiological role for the GABA and its receptors in the PNS might be hypothesised. In particular, we have demonstrated that the selective ligands of the GABA-A and GABA-B receptors, respectively muscimol and baclofen, control the Schwann cell proliferation and the expression of some specific myelin proteins (e.g. glycoprotein P0, peripheral myelin protein 22, PMP22, connexin 32, myelin associated glycoprotein, MAG). Moreover, we have also reported that some neuroactive steroids, such as the allopregnanolone (THP) and androstenediol (3alpha-diol), known to be allosteric modulator of the GABA-A receptor, are able to control the PMP22 synthesis in the Schwann cell. In addition, we have recently observed that THP is the main modulator of the different GABA-B subunit (i.e. 1a, 1b, 2) expressions in the Schwann cells; some of these effects are mimicked by muscimol and GABA, indicating a GABA-A mediated effects in such a control. Collectively, our observations suggest that, in the PNS, the cross-talk between the GABAergic system (via the GABA-A and GABA-B receptors) and the neuroactive steroids may play an important role in the neuron-Schwann cell interactions, which are modified in case of peripheral degenerative neuropathies. (Supported by E.C. QLK6-CT-2000-00179)