NE耦联异常表达Nav1.8在面神经异位动作电位产生中的作用

Hemifacial spasm (HFS) is one of the cranial nerve hyperexcitability disorders, which has been confirmed to be caused by vascular compression of the nerve root. Despite demyelinations were found in the facial nerve fibers, the mechanism of the disease has been unclear so far. Our pilot studies showed: 1) abrasion of the offending artery wall was also necessary to development of the disease; 2) abnormal expression of Nav1.8 in the facial nerve was found in the HFS animal model; 3) the abnormal muscle response (AMR) could be induced by norepinephrine (NE). Accordingly, we propose a novel hypothesis on the mechanism of HFS. The neurovascular conflict may give rise to lesions of both the artery and the nerve, and cause emersion of transmembrane proteins (receptors and iron channels) from the nerve fibers and spillover of neurotransmitters released from the sympathetic endings from the offending artery wall. When these neurotransmitters transmitted to the facial nerve in close contact, they would bind to the receptors. Through the G-protein coupled receptors, the Na+ channels could be activated and cause subthreshold membrane potential oscillation in the facial nerve, which may lead to generation of ectopic action potential. When these ectopic impulses extended to the neuromuscular junctions in the face, involuntary contractions of facial muscles occurred. To prove our hypothesis, we will use ELISA, laser confocal microscope, Western Blot and RT-PCR, multi-tube microelectrode and EMG to measure the neurotransmitters released from the offending artery wall, to observe and analyze those transmembrane proteins merged from the damaged nerve, to record the resting membrane potential and action potential as well as AMR, respectively. Meanwhile, receptor antagonists, siRNA interference and gene knockout were also used to disprove. In this project, neurotransmitters from the offending artery and transmembrane proteins developed in the facial nerve were first focused on. Our study would provide insights into the pathogenesis regarding the cranial nerves hyperexcitability diseases in the future.

面肌痉挛(HFS)在颅神经高兴奋性疾病中最为常见，研究认为面神经根受脑血管压迫导致脱髓鞘变性而产生异常冲动，但机制仍不详。我们的预实验发现：责任血管壁磨损也是该病发生的必要条件；模型动物面神经上有Nav1.8异常表达；去甲肾上腺素(NE)可诱发面神经AMR。由此推测：责任血管壁交感神经末梢释放的递质可能与面神经受损后膜表面形成的跨膜受体结合，并通过G蛋白耦联激活钠通道，使处于阈下膜电位震荡的面神经轴突产生可传导的动作电位，引起面部肌群不随意收缩。本研究拟用ELISA检测责任血管壁神经递质，激光共聚焦显微镜、Western Blot和RT-PCR观察和分析面神经上的异位跨膜蛋白，多管微电极和肌电图记录电泳递质时面神经的膜静息电位、动作电位和AMR变化，并结合受体阻滞、siRNA干扰和基因敲除等反证手段，多方位验证NE和Nav1.8在HFS中的作用，为阐述颅神经高兴奋性疾病发生机制奠定基础。

面肌痉挛(HFS)是一种常见的颅神经高兴奋性疾病，其病因为面神经受责任血管压迫，但其具体发病机制尚不明。我们的提出假设：责任血管壁交感神经末梢释放的递质可能与面神经受损后膜表面形成的跨膜受体结合，并通过G蛋白耦联激活钠通道，使处于阈下膜电位震荡的面神经轴突产生可传导的动作电位，引起面部肌群不随意收缩。本研究用ELISA检测责任血管壁神经递质，激光共聚焦显微镜、Western Blot和RT-PCR观察和分析面神经上的异位跨膜蛋白，多管微电极和肌电图记录电泳递质时面神经的膜静息电位、动作电位和AMR变化，并结合受体阻滞、siRNA干扰和基因敲除等反证手段，多方位验证NE和Nav1.8在HFS中的作用，得出了Nav1.8 可能是面肌痉挛发病机制中重要一环，为阐述颅神经高兴奋性疾病发生机制奠定基础。本课题总共发表相关SCI论文6篇。

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