Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Brain Res. 2010 Nov 29;1362:23-31. doi: 10.1016/j.brainres.2010.09.027. Epub 2010 Sep 21.
During development, the rescue of spinal motoneurons as well as sensory neurons in the dorsal root ganglion (DRG) from programmed cell death (PCD) depends on the integrity of peripheral target innervation. Following deletion of the pro-apoptotic gene Bax, both motoneurons and DRG neurons are rescued from PCD. In the present paper, we asked whether different cell types in the DRG exhibit distinct responses to Bax deletion. In 1-month-old Bax-deficient (Bax-/-) mice, distinct subsets of DRG neurons that were immunopositive for TrkA, CGRP, TRPV1 or TrkC, were all increased in number and exhibited cell atrophy compared to wild type DRG neurons. In addition there was hyperinnervation of the epidermis by CGRP immunopositive processes and a correlated functional hypersensitivity of mechanical nociception in Bax-/- mice. By contrast, the functional properties of populations of rescued thermoreceptor and mechanoreceptor DRG neurons were unchanged. These data indicate that although Bax deletion rescues all of the DRG cell types examined here from PCD, the functional consequences of having excess cells differ between sensory phenotypes.
在发育过程中，脊髓运动神经元和背根神经节（DRG）中的感觉神经元免于程序性细胞死亡（PCD）的拯救依赖于周围靶神经支配的完整性。在凋亡前基因 Bax 缺失后，运动神经元和 DRG 神经元都免于 PCD。在本研究中，我们询问了 DRG 中的不同细胞类型对 Bax 缺失的反应是否不同。在 1 月龄 Bax 缺陷型（Bax-/-）小鼠中，TrkA、CGRP、TRPV1 或 TrkC 免疫阳性的 DRG 神经元的不同亚群数量增加，与野生型 DRG 神经元相比表现出细胞萎缩。此外，CGRP 免疫阳性的过程对表皮的过度支配，以及 Bax-/-小鼠机械性伤害感受的功能超敏性相关。相比之下，被拯救的热敏和机械感受器 DRG 神经元的种群的功能特性没有改变。这些数据表明，尽管 Bax 缺失挽救了这里检查的所有 DRG 细胞类型免于 PCD，但具有多余细胞的功能后果在感觉表型之间存在差异。
