First Author | Wang Q | Year | 2021 |
Journal | Nat Commun | Volume | 12 |
Issue | 1 | Pages | 3321 |
PubMed ID | 34059669 | Mgi Jnum | J:342000 |
Mgi Id | MGI:6713994 | Doi | 10.1038/s41467-021-23843-0 |
Citation | Wang Q, et al. (2021) Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice. Nat Commun 12(1):3321 |
abstractText | 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 Ca(2+) release from intracellular Ca(2+) 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. |