Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors
Abstract
Extracellular ATP is a widespread cell-to-cell signaling molecule in the brain, where it functions as a neuromodulator by activating glia and neurons. Although ATP exerts multiple effects on synaptic plasticity and neuro-glia interactions, as well as in mood disorders, the source and regulation of ATP release remain to be elaborated. Here, we define Calhm2 as an ATP-releasing channel protein based on in vitro and in vivo models. Conventional knockout and conditional astrocyte knockout of Calhm2 both lead to significantly reduced ATP concentrations, loss of hippocampal spine number, neural dysfunction and depression-like behaviors in mice, which can be significantly rescued by ATP replenishment. Our findings identify Calhm2 as a critical ATP-releasing channel that modulates neural activity and as a potential risk factor of depression.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Astrocytes secrete adenosine ATP, which modulates depression-like behaviors.
“and secrete adenosine ATP, which modulates depression-like behaviors [65, 66].”
From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [66]
Cites
Grand challenges in global mental health
Collins, P. Y., Patel, V., Joestl, S. S., March, D., Insel, T. R., Daar, A. S., Bordin, I. A., Costello, E. J., Durkin, M., Fairburn, C., et al. (2011) · Nature · doi:10.1038/475027a · Cited by 2,043 · see citing works
Astrocytic Purinergic Signaling Coordinates Synaptic Networks
Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J.-Y., Takano, H., Moss, S. J., McCarthy, K., & Haydon, P. G. (2005) · Science · doi:10.1126/science.1116916 · Cited by 1,280 · see citing works
Surget, A., Saxe, M., Leman, S., Ibarguen-Vargas, Y., Chalon, S., Griebel, G., Hen, R., & Belzung, C. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.02.022 · Cited by 556 · see citing works
Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes
Sultan, S., Li, L., Moss, J., Petrelli, F., Cassé, F., Gebara, E., Lopatar, J., Pfrieger, F. W., Bezzi, P., Bischofberger, J., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.037 · Cited by 284 · see citing works
Grand challenges in global mental health: integration in research, policy, and practice
Collins, P. Y., Insel, T. R., Chockalingam, A., Daar, A., & Maddox, Y. T. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001434 · Cited by 220 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Di Benedetto, G., Burgaletto, C., Bellanca, C. M., Munafò, A., Bernardini, R., & Cantarella, G. (2022) · Cells · doi:10.3390/cells11172728 · Cited by 189 · see citing works
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
Karbownik, M. S., Sokołowska, P., & Kowalczyk, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076617 · Cited by 6 · see citing works
- Authors
- Jun, M., Xiaolong, Q., Chaojuan, Y., Ruiyuan, P., Shukun, W., Junbing, W., Li, H., Hong, C., Jinbo, C., Rong, W., Yajin, L., Lanqun, M., Fengchao, W., Zhiying, W., Jianxiong, A., Yun, W., Xia, Z., Chen, Z., & Zengqiang, Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Zhejiang University (CN)
- Aviation General Hospital (CN)
- University of Ottawa (CA)
- Corresponding author
- Zengqiang, Y
- Venue
- Molecular Psychiatry
- Published
- 2017-11-28
- Volume
- 23
- Issue
- 4
- Pages
- 883-891
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2768386445
- Cited by
- 95
- References
- 5
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 19 · 2023: 11 · 2022: 11 · 2021: 15 · 2020: 17 · 2019: 3
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-01-09)
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- astrocytes, extracellular ATP release, depression-like behavior, mood disorders, neuronal activity
- MeSH terms
- Adenosine Triphosphate, Animals, Astrocytes, Brain, Depression, Depressive Disorder, Disease Models, Animal, Hippocampus, Male, Mice, Inbred C57BL, Neuroglia, Neuronal Plasticity, Neurons, Risk Factors, Calcium Channels, Signal Transduction, Mice, Knockout, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
