運動神經元NRIP對運動神經及肌肉的影響

Abstract

核受體交互蛋白（NRIP）為一多功能蛋白，於骨骼肌與脊髓中均有表現，參與神經肌肉接點（NMJ）穩定維持。肌肉來源的NRIP功能已有相關研究，但神經元來源NRIP（mnNRIP）的生理角色仍未釐清。本研究目的為探討mnNRIP對NMJ穩定與神經再生之貢獻。我們利用運動神經元專一性NRIP剔除小鼠（mnKO）模型，分析其脊髓中運動神經元形態、NMJ結構、運動行為與坐骨神經損傷後的再生狀態。結果發現，mnKO小鼠脊髓中大型膽鹼能神經元明顯減少，但其NMJ結構、肌纖維類型及運動功能與野生型無顯著差異。坐骨神經損傷後14天，mnKO與對照組皆展現類似的NMJ再生能力。值得注意的是，mnKO小鼠在未受傷對側肢體出現提早去神經化現象，顯示mnNRIP可能於壓力狀態下支持雙側NMJ的穩定性。總結而言，mnNRIP雖非維持NMJ結構及再生所必需，但可能參與運動神經元存活及傷後跨側神經反應之調控。

NRIP is a multifunctional protein expressed in muscle and spinal cord, implicated in neuromuscular junction (NMJ) maintenance. While muscle-derived NRIP supports NMJ stability, its motor neuron-derived counterpart (mnNRIP) is less studied. We aimed to determine the physiological function of mnNRIP in NMJ homeostasis and regeneration. By generating mnNRIP knockout (mnKO) mice, we examined motor neuron morphology, NMJ structure, behavioral performance, and regenerative capacity following sciatic nerve injury. mnKO mice exhibited reduced numbers of large spinal cholinergic neurons but displayed no significant changes in NMJ architecture, muscle fiber composition, or motor behavior. At 14 days after nerve injury, both mnKO and wild-type mice showed comparable NMJ regeneration. Unexpectedly, mnKO mice exhibited early signs of NMJ denervation in the contralateral, uninjured limb. These results indicate that mnNRIP is not essential for NMJ regeneration or structure under normal conditions but may play a role in supporting bilateral NMJ integrity under stress. Thus, mnNRIP contributes to motor neuron maintenance and may regulate trans-neural responses to injury.