胶质细胞Kir4.1调控神经损伤后口腔颌面部感觉功能异常的研究

神经损伤引起的感觉功能异常是口腔临床常见的严重并发症。本课题组在前期工作基础上，结合神经科学相关研究进展提出，胶质细胞上内向整流性钾通道4.1（Kir4.1）是调控神经损伤后口颌面感觉功能异常的潜在重要机制。本项目拟围绕上述机制在三叉神经系统外周敏化和中枢敏化过程中的作用，进一步开展以下研究：①通过构建Kir4.1相关模式动物，建立神经损伤模型，分析外周和中枢主要胶质细胞上Kir4.1的变化特点，及其与感觉功能改变的关系；②在外周敏化方面，重点研究三叉神经节内卫星胶质细胞上Kir4.1调控神经元胞外钾平衡，影响神经兴奋性的机制；③在中枢敏化方面，重点分析延髓三叉神经脊束核尾侧亚核内，星形胶质细胞上Kir4.1对神经元兴奋性、突触传递和可塑性的影响。本项目的实施，可以为口腔临床中神经损伤导致感觉功能异常的机制和干预研究提供新思路，也为相关学科交叉领域的共性问题研究提供新依据。

Sensory impairment caused by nerve injury is a common and serious complication associated with dental therapy. Recent neuroscience findings have pointed out that the inwardly rectifying potassium channel 4.1 (Kir4.1) on the peripheral and central glial cells plays a crucial role in the abnormal sensation in oral and maxillofacial regions. In our previous studies, it was also found that potassium balance was the major factor mediating the cross-talk between the trigeminal ganglion neurons and satellite glial cells after constriction injury to inferior alveolar nerve. Therefore, in this project, we aim to clarify the effects of Kir4.1 on key glial cells during the peripheral and central sensitization process of the trigeminal nervous system after peripheral nerve injury. This project intends to include following parts: ①Establish the animal models of dental nerve injury to study the characteristics and connection between the nerve injury pathology and neurosensory impairment. ②At the peripheral sensitization level, observe the role of Kir4.1 on satellite glial cells in the regulation of neuron excitability within the trigeminal ganglion after nerve injury. ③At the central sensitization level, observe the synapse activity changes in spinal trigeminal nucleus caudalis induced by the Kir4.1 on the astrocytes. The findings of this projects might not only reveal the key mechanisms and possible treatment targets of the dental injury related neurosensory impairment, but also provide new thoughts for the common research topics in the interdisciplinary fields.