星型胶质细胞Kir4.1通道调控MPB-PVN通路介导癫痫小鼠抑郁样行为的研究

癫痫是最常见的神经系统疾病之一，而抑郁症是其最常见的精神共患病。癫痫伴发抑郁不仅会加重癫痫发作程度，还会增加患者不良预后风险，严重者甚至引发自杀行为。目前为止，二者共患机制仍不明确。内侧臂旁核（MPB）是调节睡眠的重要核团，接受癫痫相关脑区投射并与抑郁相关的下丘脑室旁核（PVN）有往返纤维投射。而MPB在癫痫伴抑郁中的作用未见研究报道。我们前期研究证实慢性期癫痫模型小鼠具有抑郁样行为表现，癫痫可受累至MPB并导致MPB神经元兴奋性增加。因此，本课题采用匹鲁卡品诱导癫痫模型，利用光遗传学、膜片钳以及免疫荧光染色等技术，观察MPB内Kir4.1通道表达情况及MPB-PVN通路活动状况。拟证明癫痫引发MPB星形胶质细胞Kir4.1通道表达降低，从而增加MPB神经元兴奋性，以致MPB-PVN通路过度激活是癫痫伴发抑郁的重要诱因。希望为阐明癫痫伴抑郁的发病机制和临床治疗提供新的思路和理论依据。

Epilepsy is one of the most common neurological disorders, and depression is the most common mental comorbidity in epileptic patients. Epilepsy combined with depression not only exacerbates seizures, but also increases the risk of poor prognosis and even triggers suicidal behavior in severe cases. However, the mechanism of their comorbidity remains unclear so far. The medial parabrachial nucleus (MPB) is an important nucleus that regulates sleep, receives projections from epilepsy-related brain regions and has round-trip fiber projections to the hypothalamic paraventricular nucleus (PVN) associated with depression. The role of MPB in epilepsy with depression has not been reported in studies. Our previous study confirmed that the model mice with chronic-phase epilepsy exhibit depression-like behavior and that epilepsy can be affected to the MPB and lead to increased excitability of MPB neurons. Therefore, in this study, a pilocarpine-induced epilepsy model was used to observe the expression of Kir4.1 channel in MPB and the activity status of MPB-PVN pathway using optogenetics, patch clamp and immunofluorescence staining techniques. It is proposed to demonstrate that epilepsy leads to decreased expression of the Kir4.1 channel in MPB astrocytes, which increases MPB neuronal excitability such that hyperactivation of the MPB-PVN pathway is an important cause of epilepsy with depression. We hope to provide new ideas and theoretical basis for the elucidation of the pathogenesis and clinical treatment of epilepsy with depression.