Liu Jie, Yu Enyan
The Second Clinical Medical College of Zhejiang Chinese Medical University, Hanzhou 310053, China.
Department of Clinical Psychology, Zhejiang Cancer Hospital, Hanzhou 310012, China.
Curr Neurovasc Res. 2022;19(3):267-274. doi: 10.2174/1567202619666220829110111.
Depression is a class of important mental illness, which has become a severe health problem perplexing the world due to its high morbidity rate, high disability rate, and great disease burden. This study aimed to evaluate the role and possible mechanisms of P2RY12 in the depression-like behaviors model.
Serum samples of patients with depression-like behaviors were used to analyze the expression of P2RY12. Models of mice were given LPS via intraperitoneal injection for 7 days. Behavioral tests were executed in this experiment.
The expression of P2RY12 in models of depression-like behaviors or mice with depression- like behaviors were induced. The inhibition of P2RY12 presents depression-like behaviors and reduces inflammation in the model of depression-like behaviors. P2RY12 induced NLRP3 expression and suppressed NLRP3 ubiquitination in a model of depression-like behavior. The inhibition of NLRP3 reduced the effects of P2RY12 in mice model of depression-like behaviors. The regulation of NLRP3 controlled the effects of the P2RY12 in vitro model of depression-like behaviors.
We conclude that P2RY12 increased neuroinflammation to accelerate depression-like behaviors by NLPR3 inflammasome, providing novel information for the treatment of depressionlike behaviors.
抑郁症是一类重要的精神疾病,因其高发病率、高致残率和巨大的疾病负担,已成为困扰全球的严重健康问题。本研究旨在评估P2RY12在抑郁症样行为模型中的作用及可能机制。
使用具有抑郁症样行为患者的血清样本分析P2RY12的表达。通过腹腔注射给予小鼠LPS 7天以建立模型。在本实验中进行行为测试。
在抑郁症样行为模型或具有抑郁症样行为的小鼠中诱导了P2RY12的表达。抑制P2RY12会呈现出抑郁症样行为,并减少抑郁症样行为模型中的炎症。在抑郁症样行为模型中,P2RY12诱导NLRP3表达并抑制NLRP3泛素化。抑制NLRP3可降低P2RY12在抑郁症样行为小鼠模型中的作用。在抑郁症样行为的体外模型中,对NLRP3的调节控制了P2RY12的作用。
我们得出结论,P2RY12通过NLPR3炎性小体增加神经炎症以加速抑郁症样行为,为治疗抑郁症样行为提供了新的信息。