期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-021-23843-0
关键词
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资金
- National Natural Science Foundation of China [31830033, 82090032, 81971080]
- NSFC-Guangdong Joint Fund [U20A6005]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT_16R37]
- Key-Area Research and Development Program of Guangdong Province [2018B030334001]
Astrocytes play a role in the pathophysiology of autism spectrum disorder (ASD). The study demonstrates that IP3R2 conditional KO mice exhibit ASD-like behaviors, and identifies astrocyte-derived ATP as a modulator of these behaviors in mice.
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD. Astrocytes contribute to autism spectrum disorder (ASD) pathophysiology. Here, the authors show that IP3R2 conditional KO mice show ASD-like behaviours and identify astrocyte-derived ATP as a modulator of these behaviours in mice.
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