Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy.
Mol Neurobiol. 2019 Feb;56(2):1461-1474. doi: 10.1007/s12035-018-1158-x. Epub 2018 Jun 12.
GABA-B receptors are important for Schwann cell (SC) commitment to a non-myelinating phenotype during development. However, the P0-GABA-B1 conditional knockout mice, lacking the GABA-B1 receptor specifically in SCs, also presented axon modifications, suggesting SC non-autonomous effects through the neuronal compartment. In this in vitro study, we evaluated whether the specific deletion of the GABA-B1 receptor in SCs may induce autonomous or non-autonomous cross-changes in sensory dorsal root ganglia (DRG) neurons. To this end, we performed an in vitro biomolecular and transcriptomic analysis of SC and DRG neuron primary cultures from P0-GABA-B1 mice. We found that cells from conditional P0-GABA-B1 mice exhibited proliferative, migratory and myelinating alterations. Moreover, we found transcriptomic changes in novel molecules that are involved in peripheral neuron-SC interaction.
GABA-B 受体对于施万细胞(SC)在发育过程中向非髓鞘形成表型的分化具有重要作用。然而,P0-GABA-B1 条件性敲除小鼠,即特异性地在 SC 中缺乏 GABA-B1 受体,也表现出轴突改变,这表明通过神经元隔室产生了 SC 非自主性影响。在这项体外研究中,我们评估了 SC 中 GABA-B1 受体的特异性缺失是否可能诱导感觉背根神经节(DRG)神经元的自主或非自主交叉变化。为此,我们对来自 P0-GABA-B1 小鼠的 SC 和 DRG 神经元原代培养物进行了体外生物分子和转录组学分析。我们发现,条件性 P0-GABA-B1 小鼠的细胞表现出增殖、迁移和髓鞘形成改变。此外,我们发现了涉及外周神经元-SC 相互作用的新分子的转录组学变化。