Deletion of GABA-B Receptor in Schwann Cells Regulates Remak Bundles and Small Nociceptive C-fibers
Deletion of GABA-B Receptor in Schwann Cells Regulates Remak Bundles and Small Nociceptive C-fibers
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DOI：
10.1002/glia.22625
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发表时间：
2014-04-01
期刊：
影响因子：
6.2
通讯作者：
Magnaghi, Valerio
中科院分区：
文献类型：
--
作者：
Faroni, Alessandro;Castelnovo, Luca Franco;Magnaghi, Valerio
调节分化为非髓鞘雪旺细胞的机制尚不完全清楚。最近的证据表明 GABA-B 受体可能调节周围神经系统的髓鞘形成和伤害感受。 GABA-B 受体完全敲除小鼠的外周髓鞘表现出形态和分子变化。小有髓纤维的数量较多，并且与疼痛敏感性改变相关。在此，我们分析了这些变化是否可能是由于雪旺细胞中 GABA-B 受体的特异性缺失而产生的。条件小鼠 (P0-GABA-B1(fl/fl)) 显示出一种形态表型，其特征是小的无髓鞘纤维和 Remak 束（包括伤害性 C 纤维）数量的特殊增加。 P0-GABA-B1(fl/fl) 小鼠存在痛觉过敏和异常性疼痛。在这些小鼠中，形态和行为的变化与神经中神经调节蛋白 1 表达的下调有关。我们的研究结果表明，疼痛敏感性的改变源于施万细胞特异性 GABA-B 受体功能的丧失，表明 GABA-B 受体在调节施万细胞向非髓鞘形成表型成熟中发挥作用。 GLIA 2014；62:548-565
The mechanisms regulating the differentiation into non-myelinating Schwann cells is not completely understood. Recent evidence indicates that GABA-B receptors may regulate myelination and nociception in the peripheral nervous system. GABA-B receptor total knock-out mice exhibit morphological and molecular changes in peripheral myelin. The number of small myelinated fibers is higher and associated with altered pain sensitivity. Herein, we analyzed whether these changes may be produced by a specific deletion of GABA-B receptors in Schwann cells. The conditional mice (P0-GABA-B1(fl/fl)) show a morphological phenotype characterized by a peculiar increase in the number of small unmyelinated fibers and Remak bundles, including nociceptive C-fibers. The P0-GABA-B1(fl/fl) mice are hyperalgesic and allodynic. In these mice, the morphological and behavioral changes are associated with a downregulation of neuregulin 1 expression in nerves. Our findings suggest that the altered pain sensitivity derives from a Schwann cell-specific loss of GABA-B receptor functions, pointing to a role for GABA-B receptors in the regulation of Schwann cell maturation towards the non-myelinating phenotype. GLIA 2014;62:548-565