Ni Jianshu, Suzuki Takahisa, Karnup Sergei V, Gu Baojun, Yoshimura Naoki
Department of Urology, University of Pittsburgh, Pittsburgh, School of Medicine, PA, USA; Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Urology, University of Pittsburgh, Pittsburgh, School of Medicine, PA, USA.
Life Sci. 2022 Jun 1;298:120524. doi: 10.1016/j.lfs.2022.120524. Epub 2022 Mar 31.
To investigate the effect of nerve growth factor (NGF) neutralization on Na channel plasticity of bladder afferent neurons in mice with spinal cord injury (SCI).
Female C57/BL6 mice were randomly divided into spinal intact (SI) group, SCI group and SCI + NGF-Ab group. SCI was induced by spinal cord transection at the Th8/9 level. In SCI + NGF-Ab group, anti-NGF antibodies (10 μg·kg-1 per hour) were continuously administered for 2 weeks using osmotic pumps. Bladder afferent neurons were labelled with Fluoro‑gold (FG) injected into the bladder wall. L6-S1 dorsal root ganglion (DRG) neurons were dissociated and whole-cell patch clamp recordings were performed on FG-labelled neurons. Expression of Nav1.7 and Nav1.8 was examined by immunofluorescent staining.
Whole-cell patch clamp recordings showed that TTX only partially inhibited action potentials (AP) and Na currents of bladder afferent neurons in SI mice, but it almost completely inhibited them in SCI mice. Total and TTX-sensitive Na currents were increased and TTX-resistant currents were decreased in bladder afferent neurons from SCI mice vs. SI mice. These changes in SCI mice were significantly reversed by NGF-antibody treatment. Immunostaining results showed the increased and decreased levels of Nav1.7 and Nav1.8, respectively, in FG-labelled bladder afferent neurons in SCI mice vs. SI mice, which was significantly reversed in SCI + NGF-Ab mice.
NGF mediates the Na channel plasticity with a shift from TTX-resistant Nav1.8 to TTX-sensitive Nav1.7 in bladder afferent neurons, which could be a possible underlying mechanism of bladder afferent hyperexcitability and detrusor overactivity after SCI.
研究神经生长因子（NGF）中和对脊髓损伤（SCI）小鼠膀胱传入神经元钠通道可塑性的影响。
将雌性C57/BL6小鼠随机分为脊髓完整（SI）组、SCI组和SCI + NGF-Ab组。通过在胸8/9水平横断脊髓诱导SCI。在SCI + NGF-Ab组中，使用渗透泵以每小时10 μg·kg-1的剂量连续给予抗NGF抗体2周。将荧光金（FG）注入膀胱壁以标记膀胱传入神经元。分离L6-S1背根神经节（DRG）神经元，并对FG标记的神经元进行全细胞膜片钳记录。通过免疫荧光染色检测Nav1.7和Nav1.8的表达。
全细胞膜片钳记录显示，TTX仅部分抑制SI小鼠膀胱传入神经元的动作电位（AP）和钠电流，但几乎完全抑制SCI小鼠的动作电位和钠电流。与SI小鼠相比，SCI小鼠膀胱传入神经元的总钠电流和TTX敏感钠电流增加，TTX耐药电流减少。NGF抗体治疗可显著逆转SCI小鼠的这些变化。免疫染色结果显示，与SI小鼠相比，SCI小鼠FG标记的膀胱传入神经元中Nav1.7水平升高，Nav1.8水平降低，而在SCI + NGF-Ab小鼠中这一变化得到显著逆转。
NGF介导膀胱传入神经元钠通道可塑性，使其从TTX耐药的Nav1.8转变为TTX敏感的Nav1.7，这可能是SCI后膀胱传入神经过度兴奋和逼尿肌过度活动的潜在机制。
