Schwann cell-axon interaction through GABA receptors : new insights from the GABA-B(1)(-/-) knockout mice

In the PNS the Schwann cells express functionally active GABAA and GABAB receptors. In particular, the GABAB -1a, -1b and -2 subunits form a receptor negatively coupled to the cAMP effector system. This receptor is a target for specific GABAB agonists (e.g. baclofen) and antagonists (e.g. CGP62349). In the PNS the activation of the GABAA and GABAB receptors controls the expression of specific myelin proteins (such as P0, PMP22, MAG, Cx32) and the Schwann cell proliferation. Therefore, a physiological role for GABA receptors in the peripheral myelination has been hypothesized. We have utilized the GABAB(1) knockout mice in order to analyze the possible biochemical and morphological changes occurring either in the myelin or in the axonal compartment of the PNS. The mRNA and protein levels of P0 and PMP22 are significantly elevated (respectively about 50% and 200%) in the (-/-) mice. The morphometric analysis revealed that the sciatic nerves of the (-/-) mice present a reduction in the diameter of the myelinated fibers and in the myelin thickness. However, (-/-) mice have an increase in the number of fibers with irregular profiles but also in the number of small axons and small neurons of the lumbar DRG. Consistent with the increased number in small myelinated fibers and the decrease in large myelinated fibers, the (-/-) mice showed gait impairment and were hyperalgesic to thermal but not to mechanical allodynic stimuli. Unexpectedly, these altered sensory functions might be related to the dysmyelination observed in the GABAB1 (-/-) mice. In conclusion, our results provide novel evidence for a role of the GABAergic signaling, mainly via GABAB receptor, in the Schwann cell-axon interaction.