小鼠青春期社会隔离抑郁模型的建立及应用

Major depressive disorder (MDD) is the most common mental disease, which is one of the reasons that cause disabilities nowadays, but their mechanisms are unknown. So far, the animal models that study the MDD have focused on adulthood. However, adolescence is also a period that MDD often happened, but no animal model studying in this period. Our preliminary study indicated that social isolation during adolescent exhibited depressive-like behaviors. Meanwhile, the number of PV interneuron and the level of NRG1 expression decreased. The present project will further determine: (1) whether social isolation during adolescent caused depressive-like behaviors; (2) the clinical antidepressants can rescue the depressive-like behaviors that caused by adolescent social isolation; (3) whether PV interneuron was involved in this process; (4) whether NRG1-ErbB4 signaling pathway mediated this process via PV interneuron. This study will construct a new animal model of depression during the adolescent period, and uncover the mechanism of MDD happened in this period, which may supply a target spot for early diagnosis and treatment for MDD.

抑郁症是最为常见的精神疾病，也是当今世界致残的一个主要原因，而目前对其发病机制仍不清楚。以往对于抑郁症的研究主要是在成年的动物模型上，而青春期也是抑郁症的高发阶段，但目前缺乏青春期抑郁动物模型。我们前期的预实验结果发现青春期小鼠经社会隔离饲养后即出现抑郁样表型，而抑郁小鼠前额叶皮层的PV中间神经元数量减少，NRG1表达降低。本项目将进一步：（1）确定青春期社会隔离对抑郁症的各种指标的影响；（2）确定常用的抗抑郁药可以逆转青春期社会隔离导致的抑郁样表型；（3）确定PV中间神经元参与调控青春期社会隔离导致的抑郁样行为；（4）确定NRG1-ErbB4信号通过PV中间神经元参与调控青春期社会隔离导致抑郁样行为；本项目将建立一种新的青春期抑郁症动物模型，揭示这个关键时间段抑郁发生的分子机制，并为抑郁症的早期发现和早期治疗提供理论依据。

抑郁症是最为常见的精神疾病，也是当今世界致残的一个主要原因，而其发病机制仍不清楚。以往对于抑郁症的研究主要是在成年的动物模型上，而青春期也是抑郁症的高发阶段，但目前缺乏青春期抑郁动物模型。我们前期的预实验结果发现青春期小鼠经社会隔离饲养后即出现抑郁样表型，而抑郁小鼠前额叶皮层的PV中间神经元数量减少，NRG1表达降低。本项目在前期的预实验结果上进一步发现：（1）青春期社会隔离导致抑郁满足表象一致性原则；（2）青春期社会隔离导致抑郁满足药物预见性原则；（3）PV中间神经元参与调控青春期社会隔离导致的抑郁样行为；（4）NRG1-ErbB4信号通过PV中间神经元参与调控青春期社会隔离导致抑郁样行为。因此，本项目建立了一种新的青春期抑郁症动物模型，并揭示这个关键时间段抑郁发生的分子机制，从而为抑郁症的早期发现和早期治疗提供理论依据。