Increased Kcnq2 in the hippocampal contributes to esketamine-induced long-term cognitive dysfunction in neonatal mice.
Journal of affective disorders June 8, 2025 Junjie Zhang, Rui Xiong, Yujuan Su et al. 1 citation
Repeated esketamine exposure during early postnatal development in mice led to significant hippocampal injury, including downregulation of glutamatergic neuronal markers and persistent cognitive dysfunction in adolescence. These adverse outcomes were strongly associated with elevated expression of Kcnq2 in the hippocampus. Both pharmacological blockade and genetic knockdown of Kcnq2 mitigated the cognitive deficits. Mechanistically, activation of Kcnq2 drove dephosphorylation of key signaling molecules within the Akt1/GSK-3β pathway. The findings identify Kcnq2 as a novel therapeutic target for preventing anesthesia-related cognitive deficits in pediatric populations.