内侧前额叶皮层参与散发型AD抑郁发生的机制

抑郁症是散发型AD（ADs）患者中最常见的神经精神症状。ADs抑郁症不同于原发性抑郁症，现有抗抑郁药已被证明疗效不佳。本课题组采用侧脑室注射链脲菌素(STZ-icv)诱导ADs模型发现，大鼠第7天就出现抑郁行为，而第14天出现伴发认知障碍的抑郁行为，并首次发现第7天出现的抑郁行为与大鼠内侧前额叶皮层(mPFC)中前炎性因子高表达、BDNF和5-HT水平降低，GluN2B表达水平增加有关。推测ADs抑郁行为可能与mPFC中前炎性因子、色氨酸代谢途径和NMDA受体通路相关。至今尚未见STZ-icv大鼠mPFC与ADs抑郁调控相关报道。本课题将以mPFC中上述信号通路为主要切入点，比较研究第7天和14天的抑郁机制异同点，探索ADs抑郁发生和发展过程中上述信号通路的交互关联机制。本研究将有助于进一步确认ADs抑郁的发病机制，为发现治疗和改善ADs抑郁症状的新策略和新的药物靶点，提供科学实验依据。

Depression is the most common neuropsychiatric symptom in patients with sporadic AD (ADs), which increases the risk of behavioral disorders and exacerbates the condition. The clinical characteristics of ADs depression are different from that of primary depression, and its pathogenesis is still unclear. Antidepressants based on the monoamine hypothesis have been shown to have poor efficacy. In our previous study, intracerebral ventricular injection of streptozcin(STZ-icv) induced ADs model rat, and it was found that the rats showed obvious depression-like behaviors on the 7th day and depressive behaviors with cognitive impairment on the 14th day. Depressive behavior on day 7 was found to be associated with high levels of preinflammatory cytokines, decreased levels of BDNF and 5-ht, and increased levels of GluN2B in the medial prefrontal cortex (mPFC). From these results, it was speculated that stz-icv induced depressive behavior of ADs rats might be related to immune inflammatory factors, tryptophan metabolism pathway and NMDA receptor pathway in mPFC. To date, there has been no report on mPFC in STZ-icv induced ADs depression regulation. In this study we will investigate the pathogenesis of ADs depression by evaluating the inflammatory factors, tryptophan metabolism pathway and NMDA signaling pathway in mPFC as the key points and provide scientific experimental data for the discovery of new treatment approaches and methods to ADs depression.