细胞外
海马结构
化学
生物化学
细胞生物学
分子生物学
生物
神经科学
作者
Qianqian Cui,Zhuang‐Li Hu,Yuan-Lang Hu,Xi Chen,Wang Ji,Li Mao,Xiao-Jia Lu,Ming Ni,Jian-Guo Chen,Fang Wang
标识
DOI:10.15252/embr.201947857
摘要
Emerging evidence implicates that low levels of ATP in the extracellular space may contribute to the pathophysiology of major depressive disorder (MDD). The concentration of extracellular ATP is regulated by its hydrolase ectonucleotide tri(di)phosphohydrolase (ENTPD). However, the role of ENTPD in depression remains poorly understood. Here we examine the role of CD39 (known as ENTPD1) in mouse depression-like behavior induced by chronic social defeat stress (CSDS). We demonstrate that CSDS enhances the expression and activity of CD39 in hippocampus. The CD39 functional analog apyrase also induces depression-like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD39 has an antidepressant-like effect via increasing hippocampal extracellular ATP concentration, accompanied with an increase in hippocampal neurogenesis and dendritic spine numbers in defeated mice. These results suggest that hippocampal CD39 contributes to CSDS-induced depression-like behavior via hydrolyzing extracellular ATP, indicating that CD39 may be a promising new target for the treatment of depression.
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