信息素MUP1经内侧前额叶皮层至脑桥核通路调控小鼠抑郁共情的研究

共情是个体之间情感传递的现象，已证实小鼠具有恐惧、痛和痒等共情，但机制尚不清楚。我们前期研究发现，与抑郁小鼠同笼饲养后，约70%正常小鼠会出现抑郁样行为即抑郁共情。高通量蛋白质谱结果显示抑郁共情小鼠内侧前额叶皮层（mPFC）的信息素蛋白—主要尿蛋白1（MUP1）表达升高；敲减mPFC脑区MUP1可以降低多巴胺转运体1（DAT1）表达，抑制多巴胺重摄取，缓解共情小鼠的抑郁样行为，提示：MUP1可能参与小鼠抑郁共情。文献报道mPFC神经元轴突可以投射至脑桥核（Pn），并且我们发现MUP1在mPFC和Pn高表达，光遗传抑制mPFC-Pn通路会诱发小鼠回避行为，提示MUP1可能通过上调mPFC的DAT1抑制mPFC-Pn通路的突触传递参与抑郁共情。本研究拟采用电生理、光遗传和行为学等方法，明确MUP1通过mPFC-Pn通路调控抑郁共情，为自闭症等共情障碍疾病的治疗提供新的理论依据。

Empathy is a phenomenon of emotional contagion between individuals. It has been proved that mice individuals could share fear, pain and itch, but its neurobiological mechanism is still covered. Our previous study found that about 70% mice became depressed when bred with a depressed cage mate. Results of high-throughput protein mass spectrometry in medial prefrontal cortex (mPFC) showed major urine protein (MUP1), an pheromone protein, was specifically increased in depression empathy mice. Knocking down MUP1 in mPFC reduced the sodium-dependent dopamine transporter (DAT1) expression, inhibited the reuptake of dopamine, and alleviated the depression-like behavior, suggesting a role of MUP1 in empathic mice with depression. It has been reported that the axons of mPFC neurons projected to the pontine nucleus (PN). We also found high MUP1 expression in mPFC and Pn. Furthermore opotogenetic suppressing mPFC-Pn pathway induced aversive behaviors. These results indicated MUP1 may suppressing synaptic transmission of mPFC-Pn pathway by up-regulating DAT1 in mPFC. In this study, electrophysiological, optogenetic and behavioral methods were used to verify MUP1 participated depression empathy by regulating mPFC-Pn excitatory neurons DAT1 level. Our research would provide new theoretical bases for treating empathy deficiency-related diseases such as autism.