从5-HTR6调控内嗅皮层-DG区LTP探究慢性癫痫共患抑郁障碍的神经网络机制

癫痫共患抑郁机制不明且缺乏有效药物。5-HTR6调节内嗅皮层-海马DG突触重塑的分子机制以及内嗅皮层5-HTR6表达影响慢性癫痫共患抑郁的神经网络机制尚不明确，成为科学问题。科学假说：5-HT重摄取抑制剂(SSRI)可缓解癫痫发作，5-HTR6参与癫痫共患抑郁；慢性颞叶癫痫可能存在海马DG区与内嗅皮层突触重塑，内嗅皮层—海马突触联系改变是抑郁障碍重要的神经环路；5-HTR6可能通过mTOR/p70S6K1调节内嗅皮层-海马突触重塑参与癫痫共患抑郁。研究思路：建立PILO慢性癫痫模型，予SSRI类药物干预、腺相关病毒包装敲减内嗅皮层5-HTR6，通过视频脑电、行为学测评、活体场电位、神经病理学方法(Golgi、透射电镜、激光共聚焦）、脑微透析-高效液相技术、分子生物学技术分析SSRI的安全及有效性，评估5-HT各受体亚型的表达，并探讨内嗅皮层5-HTR6调控海马突触重塑的神经网络分子机制。

The mechanism of comorbidity of epilepsy with depression is unknown and effective drugs are lacking. The molecular mechanism of 5-HTR6 regulating DG synaptic remodeling in the entorhinal cortex-hippocampus and the mechanism of 5-HTR6 expression in the entorhinal cortex affecting depression in patients with chronic epilepsy remain unclear, which has become a scientific issue. Scientific hypothesis: 5-HT reuptake inhibitors can alleviate epileptic seizures, 5-HTR6 is involved in epilepsy-associated depression; chronic temporal lobe epilepsy may have synaptic remodeling between DG region of hippocampus and entorhinal cortex; changes in synaptic connections between entorhinal cortex and hippocampus are important nerve circuits for depression; 5-HTR6 may regulate endo-hippocampal synaptic remodeling through mTOR/p70S6K1 to participate in epilepsy. Research ideas: Establish PILO chronic epilepsy model, give SSRI drug intervention, adeno-associated virus packaging knock down 5-HTR6 in the entorhinal cortex. Through video-EEG, behavioral assessment, in vivo field potential, neuropathology (Golgi, transmission electron microscopy, laser confocal), brain Microdialysis-High performance liquid chromatography, molecular biology technology, analyze the safety and effectiveness of SSRI, and evaluate the effects of 5-HT. The expression of somatic subtypes and the molecular mechanism of 5-HTR6 in the entorhinal cortex regulating synaptic remodeling in the hippocampus were investigated.