Hippocampal CD39/ENTPD1 promotes mouse depression‐like behavior through hydrolyzing extracellular ATP
Open accessAbstract
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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Dysregulation of extracellular ATP is involved in depression-like disorders in rodents.
“Our data further validate that the dysregulation of extracellular ATP, a significant mediator of astrocyte-neuron communications [61, 62], is involved in depression-like disorders in rodents [24, 63, 64].”
From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [64]
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“It took more than 3 weeks to achieve the effects of genetic deletion of CD39 with LV-siRNA; however, the anhedonia cannot persist for 4 weeks in CSDS mice [20]; and thus, it is difficult to evaluate the effect of LV-siCD39 on anhedonia.”
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APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline
Fang, W., Xiao, N., Zeng, G., Bi, D., Dai, X., Mi, X., Ye, Q., Chen, X., & Zhang, J. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01631-0 · Cited by 42 · see citing works
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- Authors
- Cui, Q., Hu, Z., Hu, Y., Chen, X., Wang, J., Mao, L., Lu, X., Ni, M., Chen, J., & Wang, F.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Corresponding author
- Wang, Fang
- Venue
- The EMBO Reports
- Published
- 2020-03-05
- Volume
- 21
- Issue
- 4
- Pages
- e47857-e47857
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC7132197
- OpenAlex
- W3010243985
- Cited by
- 56
- References
- 9
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 3 · 2020: 6
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- PCSIRT (IRT13016)
- Program for HUST Academic Frontier Youth Team (2017QYTD17)
- Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST
- National Natural Science Foundation of China (81721005, 81473199, 81671438, 81673414)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- CD39, extracellular ATP, depression, chronic social defeat stress, hippocampus, apyrase, neurogenesis, dendritic spines, antidepressant targets
- MeSH terms
- Adenosine Triphosphate, Animals, Apyrase, Depression, Major Depressive Disorder, Hippocampus, Mice, Inbred C57BL, Mice
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