Astroglial dysfunctions drive aberrant synaptogenesis and social behavioral deficits in mice with neonatal exposure to lengthy general anesthesia

by Bin Zhou, Lingmin Chen, Ping Liao, Lu Huang, Zhuo Chen, Daqing Liao, Linghui Yang, Jing Wang, Guoqiang Yu, Li Wang, Jianguo Zhang, Yunxia Zuo, Jin Liu, Ruotian Jiang

Lengthy use of general anesthetics (GAs) causes neurobehavioral deficits in the developing brain, which has raised significant clinical concerns such that the United States Food and Drug Administration (FDA) is warning on the use of GAs in children younger than 3 years. However, the molecular and cellular mechanisms for GAs-induced neurotoxicity remain largely unknown. Here, we report that sevoflurane (Sevo), a commonly used GA in pediatrics, caused compromised astrocyte morphogenesis spatiotemporally correlated to synaptic overgrowth, with reduced synaptic function in developing cortex in a regional-, exposure-length-, and age-specific manner. Sevo disrupted astrocyte Ca2+ homeostasis both acutely and chronically, which led to the down-regulation of Ezrin, an actin-binding membrane-bound protein, which we found was critically involved in astrocyte morphogenesis in vivo. Importantly, overexpression of astrocyte Ezrin rescued astrocytic and neuronal dysfunctions and fully corrected deficits in social behaviors in developing mice with lengthy Sevo exposure. Our data uncover that, in addition to neurons, astrocytes may represent important targets for GAs to exert toxic effects and that astrocyte morphological integrity is crucial for synaptogenesis and neurological behaviors.

Source link

Related posts

Allosteric mechanisms underlying the adaptive increase in hemoglobin-oxygen affinity of the bar-headed goose [RESEARCH ARTICLE]


Preservation of myocardial contractility during acute hypoxia with OMX-CV, a novel oxygen delivery biotherapeutic


<i>Plasmodium vivax</i>-like genome sequences shed new insights into <i>Plasmodium vivax</i> biology and evolution


This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy