Molecular Mechanisms of Propofol-Induced Cognitive Impairment: Suppression of Critical Hippocampal Pathways

Abstract

Propofol, a commonly used anesthetic, is known to cause postoperative cognitive dysfunction (POCD), particularly after prolonged or high-dose administration. Its effects on neural remodeling in the hippocampal region, which is vital for cognitive function, remain poorly understood. This study employs single-cell RNA sequencing (scRNA-seq) and high-throughput transcriptomic analysis to elucidate the molecular mechanisms by which propofol impairs hippocampal neural remodeling. Our findings indicate that propofol suppresses the (5-Hydroxytryptamine Receptor 1A/Glutamate Receptor 2/Phosphoinositide 3-Kinase Regulatory Subunit 1) HTR1A/GRIA2/PIK3R1 signaling pathway, contributing to cognitive dysfunction in mice. In vitro experiments reveal that propofol treatment reduces the expression of HTR1A/GRIA2/PIK3R1-related factors, decreases neuronal activity and synaptic plasticity, and increases apoptosis and inflammation. In vivo experiments demonstrate significant impairments in spatial memory and learning abilities in mice treated with propofol. These results provide new insights into the long-term effects of anesthetic drugs and offer a scientific basis for their judicious use in clinical practice. The study highlights potential strategies and targets for preventing and treating POCD, emphasizing the importance of understanding the molecular mechanisms underlying anesthetic-induced cognitive dysfunction.