Dynamic expression of estrogen receptor subtypes during brain development and their mechanistic roles in anesthetic-induced cognitive dysfunction: a review

Abstract Estrogen receptor subtypes exhibit dynamic spatiotemporal differences across stages of brain development, forming a molecular basis for the regulation of neurogenesis, synaptic plasticity, and cognitive function. Commonly used general anesthetics can disrupt endogenous estrogen signaling pathways in the brain and contribute to the development of perioperative neurocognitive disorders. This review summarizes the expression dynamics and signal transduction mechanisms of estrogen receptor subtypes from the perinatal period to old age in cognition-related brain regions, including the hippocampus and prefrontal cortex, with a particular focus on the relationship between the molecular mechanisms of anesthetic-induced cognitive impairment and the dynamic expression of estrogen receptors. It further analyzes sex- and age-related differences in anesthetic neurotoxicity and indicates that the developing and aging brain may be more susceptible to injury because of the vulnerability of estrogen signaling homeostasis. It also summarizes current research limitations and proposes that future studies should integrate cell‑specific gene editing, brain organoids, and clinical cohort investigations.