Impaired Synaptic Plasticity Mediated by Decreased GLUT1 in Hippocampal Astrocytes is Involved in Postoperative
Zi-Yi Li1, Qiang Liu1,2, Xiao-Tian Shi3
1Jiangsu Province Key Laboratory of Anesthesiology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China.
Abstract:
Postoperative cognitive dysfunction (POCD) is a common post-anesthesia complication in elderly patients characterized by impaired learning and memory function, with largely unclear neural mechanisms. This study aims to examine how Glucose transporter1 (GLUT1) affects the cognitive function changes in elderly mice with POCD by focusing on hippocampal astrocytes. GLUT1 on hippocampal astrocytes is crucial for brain glucose metabolism, and altered GLUT1 expression may affect the brain's energy supply and utilization, impacting synaptic plasticity and cognitive function. In this study, we found elderly mice developed POCD 1 day post-operation, showing reduced levels of GLUT1 expression on hippocampal astrocytes and decreased energy supply in the hippocampus. Meanwhile, the density of dendritic spines of hippocampal neurons notably decreased, resulting in impaired structural and functional plasticity. In the intervention experiment, overexpression of GLUT1 on hippocampal astrocytes alleviated the above neural dysfunction; besides, the hippocampal-dependent learning and memory impairment 1 day after anesthesia/surgery in mice were significantly improved. Briefly, we demonstrate that GLUT1 plays a crucial part in the development of POCD in elderly mice, indicating that it could be a valuable target for diagnosing and treating POCD.
