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Hippocampal CD 39/ ENTPD 1 promotes mouse depression‐like behavior through hydrolyzing extracellular ATP
Author(s) -
Cui QianQian,
Hu ZhuangLi,
Hu YuanLang,
Chen Xi,
Wang Ji,
Mao Li,
Lu XiaoJia,
Ni Ming,
Chen JianGuo,
Wang Fang
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201947857
Subject(s) - extracellular , hippocampal formation , chemistry , biochemistry , microbiology and biotechnology , biology , neuroscience
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 CD 39 (known as ENTPD 1) in mouse depression‐like behavior induced by chronic social defeat stress ( CSDS ). We demonstrate that CSDS enhances the expression and activity of CD 39 in hippocampus. The CD 39 functional analog apyrase also induces depression‐like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD 39 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 CD 39 contributes to CSDS ‐induced depression‐like behavior via hydrolyzing extracellular ATP , indicating that CD 39 may be a promising new target for the treatment of depression.