Altered peripheral myelination in mice lacking GABAB receptors

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Abstract

Emerging evidence implicates γ-aminobutyric acid type B (GABAB) receptors in peripheral nervous system (PNS) functions. In order to elucidate which biochemical, morphological and functional parameters of peripheral nerve fibers depend on GABAB receptors we studied GABAB1-deficient mice, which are devoid of functional GABAB receptors. Here, we show that GABAB1-deficient mice exhibit morphological and molecular changes in peripheral myelin, including an increase in the number of irregular fibers and increases in the expression levels of the myelin proteins PMP22 and P0. Moreover, the number of small myelinated fibers and small neurons of the lumbar dorsal root ganglia is higher in GABAB1-deficient mice than in wild-type littermates. We further show that GABAB1-deficient mice exhibit gait alterations and reduced allodynia. In summary, our findings implicate GABAB receptors in the PNS myelination process and raise the possibility that PNS alterations contribute to the sensory phenotypes of GABAB1-deficient mice.

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