Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice

Abstract

The elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibial fracture surgery, a common model of postoperative cognitive dysfunction in aged mice. We used Golgi staining and neuroelectrophysiological techniques to detect structurally and functionally impaired synaptic plasticity in hippocampal CA1 region of Postoperative cognitive dysfunction aged mice, respectively. Based on the ‘third party synapse’ hypothesis of astrocytes, we used glial fibrillary acidic protein to label astrocytes and found an increase in abnormal activation of astrocytes in the CA1 region of hippocampus. We hypothesize that abnormal astrocyte function is the driving force for impaired synaptic plasticity. So we used chemogenetic methods to intervene astrocytes. Injection of adeno-associated virus into the CA1 region of the hippocampus bilateral to aged mice resulted in the specific expression of the Gq receptor, a receptor specially designed to be activated only by certain drugs, within astrocytes. The results of novel object recognition and conditioned fear experiments showed that CNO activation of astrocyte Gq pathway could improve the learning and memory ability and the synaptic plasticity of Postoperative cognitive dysfunction aged mice was also improved. The results of this study suggest that activation of the Gq pathway in astrocytes alleviates Postoperative cognitive dysfunction induced by anesthesia and surgery in aged mice.