The p75 neurotrophin receptor (p75^NTR) is required for maintaining peripheral sensory neuron survival and function; however, the underlying cellular mechanism remains unclear. The general view is that expression of p75^NTR by the neuron itself is required for maintaining sensory neuron survival and myelination in the peripheral nervous system (PNS). Adopting a neuronal‐specific conditional knockout strategy, we demonstrate the partial depletion of p75^NTR in neurons exerts little influence upon maintaining sensory neuron survival and peripheral nerve myelination in health and after demyelinating neuropathy. Our data show that the density and total number of dorsal root ganglion (DRG) neurons in 2‐month‐old mice is not affected following the deletion of p75^NTR in large‐diameter myelinating neurons, as assessed by stereology. Adopting experimental autoimmune neuritis induced in adult male mice, an animal model of demyelinating peripheral neuropathy, we identify that deleting p75^NTR in myelinating neurons exerts no influence upon the disease progression, the total number of DRG neurons, and the extent of myelin damage in the sciatic nerve, indicating that the expression of neuronal p75^NTR is not essential for maintaining peripheral neuron survival and myelination after a demyelinating insult in vivo. Together, results of this study suggest that the survival and myelination of peripheral sensory neurons is independent of p75^NTR expressed by a subtype of neurons in vivo. Thus, our findings provide new insights into the mechanism underpinning p75^NTR‐mediated neuronal survival in the PNS.

中文翻译：

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大直径 DRG 神经元中 p75NTR 的部分缺失对 体内 外周感觉神经元的存活没有影响。

p75 神经营养因子受体 (p75 ^NTR ) 是维持外周感觉神经元存活和功能所必需的；然而，潜在的细胞机制仍不清楚。一般的观点是，神经元本身表达 p75 ^NTR是维持周围神经系统 (PNS) 中感觉神经元存活和髓鞘形成所必需的。采用神经元特异性条件性敲除策略，我们证明神经元中 p75 ^NTR的部分消耗对维持健康和脱髓鞘神经病变后的感觉神经元存活和周围神经髓鞘形成几乎没有影响。我们的数据显示，删除 p75 后，2 个月大小鼠的背根神经节 (DRG) 神经元的密度和总数不受影响通过体视学评估的大直径髓鞘神经元中的^NTR。采用在成年雄性小鼠中诱导的实验性自身免疫性神经炎，脱髓鞘周围神经病变的动物模型，我们发现在髓鞘神经元中删除 p75 ^NTR对疾病进展、DRG 神经元总数和髓鞘损伤程度没有影响。坐骨神经，表明神经元 p75 ^NTR的表达对于体内脱髓鞘损伤后维持外周神经元存活和髓鞘形成不是必需的。总之，这项研究的结果表明，外周感觉神经元的存活和髓鞘形成与神经元亚型表达的 p75 ^NTR无关体内。因此，我们的研究结果为 P75 ^NTR介导的 PNS 中神经元存活的机制提供了新的见解。