PTEN and Cognitive impairment: Erα activation with PPT suppressed PTEN nuclear translocation, preserved synaptic structure, and improved cognitive function, whereas AAV<sub>shAagab</sub> largely abolished these protective effects.<h4>Conclusion</h4>Our study demonstrates that PTEN nuclear translocation mediates sevoflurane-induced synaptic and cognitive deficits in aged female mice, and that Erα activation mitigates these effects by modulating PTEN localization.