Molecular Insights into Propofol’s Neurotoxic Effects: Targeting the HTR1A/cAMP Signaling Pathway

Propofol, a commonly used anesthetic in clinical practice, is favored for its rapid onset and short duration of action. Despite its widespread use, the potential neurotoxic effects of propofol remain insufficiently understood. This study utilized high-throughput transcriptome sequencing and network pharmacology to investigate the mechanisms by which propofol induces neurotoxicity in rat hippocampal neural progenitor cells (NPCs), focusing on the HTR1A/cAMP signaling pathway. Our findings reveal that propofol significantly inhibits the HTR1A/cAMP pathway, leading to altered expression of key genes that affect neuronal activity, inflammatory responses, and apoptosis. In vivo experiments further demonstrate that propofol impairs spatial learning and memory in rats, an effect that is partially reversed by overexpression of HTR1A. These results not only elucidate the molecular mechanisms underlying propofol-induced neuronal damage but also provide critical insights into the safe application of propofol in clinical settings.