Peripheral injury of pelvic visceral sensory nerves alters GFRα (GDNF family receptor alpha) localization in sensory and autonomic pathways of the sacral spinal cord.

Peripheral injury of pelvic visceral sensory nerves alters GFRα (GDNF family receptor alpha) localization in sensory and autonomic pathways of the sacral spinal cord.
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DOI:
10.3389/fnana.2015.00043
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发表时间:
2015
影响因子:
2.9
通讯作者:
Osborne PB
Osborne PB
中科院分区:
医学3区
文献类型:
--
作者:
Forrest SL;Payne SC;Keast JR;Osborne PB

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GDNF(胶质细胞源性神经营养因子)、neurturin和artemin使用其共受体(分别为GFRα1、GFRα2和GFRα3)和酪氨酸激酶Ret进行下游信号传导。在啮齿类动物背根神经节(DRG)中,大多数无髓鞘和一些有髓鞘感觉传入纤维表达至少一种GFRα。这些受体的成人功能尚未完全阐明,但它们在外周神经损伤后的活性可促进外周和中枢轴突再生、感觉恢复和有助于疼痛的感觉超敏反应。我们先前对成年啮齿类动物脊髓和坐骨神经损伤的免疫组织化学研究已经确定了位于DRG的感觉神经元的中央脊髓轴突中GFRα1、GFRα2或GFRα3的特征性变化。在这里,我们通过研究骨盆和腹下神经的损伤来扩展和对比这种分析,骨盆和腹下神经包含大多数投射到骨盆内脏的感觉轴突(例如,膀胱和下肠)。在第7天,我们检测到盆神经而不是腹下神经切断对同侧脊髓的影响。在神经损伤同侧骶髓(L 6-S1),GFRα1免疫反应(IR)在内侧背角增加,CGRP-IR在外侧背角减少。盆神经损伤还上调了骶副交感神经核中的GFRα1-和GFRα3-IR终末以及GFRα1-IR神经元胞体,该神经核向盆神经提供脊髓副交感神经节前输出。这一证据表明,外周轴突切断对脊髓的躯体和内脏感觉输入有不同的影响,并确定感觉自主神经相互作用作为损伤后调节的可能位点。
GDNF (glial cell line-derived neurotrophic factor), neurturin and artemin use their co-receptors (GFRα1, GFRα2 and GFRα3, respectively) and the tyrosine kinase Ret for downstream signaling. In rodent dorsal root ganglia (DRG) most of the unmyelinated and some myelinated sensory afferents express at least one GFRα. The adult function of these receptors is not completely elucidated but their activity after peripheral nerve injury can facilitate peripheral and central axonal regeneration, recovery of sensation, and sensory hypersensitivity that contributes to pain. Our previous immunohistochemical studies of spinal cord and sciatic nerve injuries in adult rodents have identified characteristic changes in GFRα1, GFRα2 or GFRα3 in central spinal cord axons of sensory neurons located in DRG. Here we extend and contrast this analysis by studying injuries of the pelvic and hypogastric nerves that contain the majority of sensory axons projecting to the pelvic viscera (e.g., bladder and lower bowel). At 7 d, we detected some effects of pelvic but not hypogastric nerve transection on the ipsilateral spinal cord. In sacral (L6-S1) cord ipsilateral to nerve injury, GFRα1-immunoreactivity (IR) was increased in medial dorsal horn and CGRP-IR was decreased in lateral dorsal horn. Pelvic nerve injury also upregulated GFRα1- and GFRα3-IR terminals and GFRα1-IR neuronal cell bodies in the sacral parasympathetic nucleus that provides the spinal parasympathetic preganglionic output to the pelvic nerve. This evidence suggests peripheral axotomy has different effects on somatic and visceral sensory input to the spinal cord, and identifies sensory-autonomic interactions as a possible site of post-injury regulation.
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