First Author | Liu Y | Year | 2019 |
Journal | Biochem Biophys Res Commun | Volume | 519 |
Issue | 4 | Pages | 803-811 |
PubMed ID | 31558319 | Mgi Jnum | J:291418 |
Mgi Id | MGI:6444015 | Doi | 10.1016/j.bbrc.2019.09.053 |
Citation | Liu Y, et al. (2019) Hippocampal astrocyte dysfunction contributes to etomidate-induced long-lasting synaptic inhibition. Biochem Biophys Res Commun 519(4):803-811 |
abstractText | Cognitive impairments following the use of general anesthetics are well documented but the underlying mechanisms are unclear. Here, long-lasting cognitive deficits were observed in aged mice following administration of etomidate at a clinically relevant concentration (20mg/kg); these deficits were closely related to hippocampal synaptic inhibition and astrocyte dysfunction. Using microdialysis and magnetic-activated cell-sorting techniques, we found that astrocyte secretion of glutamate, d-serine, and ATP, as well as astrocyte function, were depressed in the hippocampus following treatment with etomidate. Interestingly, hippocampal astrocyte inhibition (designer receptors exclusively activated by designer drugs; DREADDs) had no effect on the initial synaptic inhibition, but reversed synaptic and cognitive depression in the long term. Furthermore, continual activation of hippocampal astrocytes following administration of a sedative dose (8mg/kg) of etomidate induced synaptic inhibition and cognitive dysfunction. Our results indicate that general anesthetic-induced hippocampal astrocyte dysfunction plays a role in maintaining synaptic inhibition, which eventually induces long-lasting cognitive deficits. |