Jedi-1 deficiency increases sensory neuron excitability through a non-cell autonomous mechanism.
Jedi-1 deficiency increases sensory neuron excitability through a non-cell autonomous mechanism.
复制标题
Jedi-1 缺陷通过非细胞自主机制增加感觉神经元的兴奋性。
DOI：
10.1038/s41598-020-57971-2
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发表时间：
2020
影响因子：
4.6
通讯作者：
Carter,BruceD
中科院分区：
文献类型：
--
作者：
Trevisan,AlexandraJ;Bauer,MaryBeth;Brindley,RebeccaL;Currie,KevinPM;Carter,BruceD
背根神经节（DRG）容纳负责躯体感觉（包括疼痛）的初级传入神经元。我们以前确定Jedi-1（PEAR 1/MEGF 12）作为一种吞噬受体，由DRG中的卫星胶质细胞表达，参与清除发育过程中的凋亡神经元。在这里，我们进一步研究了这种受体在生存的Jedi-1基因敲除小鼠中的功能。除了卫星神经胶质细胞，我们发现Jedi-1表达在神经束膜神经胶质细胞和内皮细胞，但不是在感觉神经元。我们在Jedi-1基因敲除小鼠的神经胶质细胞或血管中没有检测到任何形态或功能变化。令人惊讶的是，我们确实观察到了DRG神经元活动的变化。在Jedi-1基因敲除（KO）小鼠的神经元中，相对于野生型（WT）对照组，辣椒素敏感细胞的比例增加。膜片钳电生理学显示兴奋性增加，KO神经元的动作电位放电模式从阶段性转变为强直性。我们还发现改变的性质的电压门控钠通道电流的Jedi-1空神经元。这些结果为Jedi-1在外周神经系统中的表达模式提供了新的见解，并表明Jedi-1的缺失通过非神经元细胞和感觉神经元之间的细胞间相互作用间接改变了DRG神经元的活性。
The dorsal root ganglia (DRG) house the primary afferent neurons responsible for somatosensation, including pain. We previously identified Jedi-1 (PEAR1/MEGF12) as a phagocytic receptor expressed by satellite glia in the DRG involved in clearing apoptotic neurons during development. Here, we further investigated the function of this receptorin vivousing Jedi-1 null mice. In addition to satellite glia, we found Jedi-1 expression in perineurial glia and endothelial cells, but not in sensory neurons. We did not detect any morphological or functional changes in the glial cells or vasculature of Jedi-1 knockout mice. Surprisingly, we did observe changes in DRG neuron activity. In neurons from Jedi-1 knockout (KO) mice, there was an increase in the fraction of capsaicin-sensitive cells relative to wild type (WT) controls. Patch-clamp electrophysiology revealed an increase in excitability, with a shift from phasic to tonic action potential firing patterns in KO neurons. We also found alterations in the properties of voltage-gated sodium channel currents in Jedi-1 null neurons. These results provide new insight into the expression pattern of Jedi-1 in the peripheral nervous system and indicate that loss of Jedi-1 alters DRG neuron activity indirectly through an intercellular interaction between non-neuronal cells and sensory neurons.