质子激活氯离子通道调节急性脊髓损伤后的运动功能

摘要(中文译文)

脊髓损伤（SCI）会破坏运动、感觉和自主神经功能，严重损害生活质量。在此，我们研究了由基因编码的质子激活氯离子（PAC）通道在SCI后运动功能恢复中的作用。我们发现PAC在脊髓中表达，主要表达于小胶质细胞，且其表达在损伤后显著增加。在基因敲除小鼠中，运动功能恢复显著改善，并伴有小胶质细胞增生减少。此外，小胶质细胞特异性敲除该基因减少了损伤体积，并进一步增强了运动功能恢复，行为学评估证实了这一点。在机制上，小胶质细胞中该基因的缺失抑制了损伤后小胶质细胞的过度激活和促炎细胞因子的释放。总之，这些发现表明PAC通道是一种损伤诱导的调节因子，可加重炎症并损害运动功能恢复。因此，靶向PAC可能是一种有前景的治疗策略，用以减轻炎症并促进SCI后的脊髓修复。

Abstract

Spinal cord injury (SCI) disrupts motor, sensory, and autonomic functions, profoundly impairing quality of life. Here, we investigate the role of the proton-activated chloride (PAC) channel, encoded by , in motor function recovery following SCI. We found that PAC is expressed in the spinal cord, predominantly in microglia, and its expression markedly increases after injury. In knockout mice, motor recovery was significantly improved, accompanied by reduced microgliosis. Moreover, microglia-specific deletion of decreased lesion volume and further enhanced motor recovery, as demonstrated by behavioral assessments. Mechanistically, loss of in microglia suppressed excessive microglial activation and the release of pro-inflammatory cytokines after injury. Together, these findings identify the PAC channel as an injury-induced regulator that aggravates inflammation and impairs motor recovery. Targeting PAC may thus represent a promising therapeutic strategy to mitigate inflammation and promote spinal cord repair after SCI.

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