TREK-1 pathway mediates isoflurane-induced memory impairment in middle-aged mice

•Memory impairment is induced by isoflurane anesthesia in middle-aged mice.•TREK-1 plays a key role in isoflurane-induced memory impairment.•Over-expression of TREK-1 exacerbates isoflurane-induced memory impairment.•Inhibition of TREK-1 attenuates isoflurane-induced memory deficits.

Post-operative cognitive dysfunction (POCD) has been widely reported, especially in elderly patients. An association between POCD and inhalational anesthetics, such as isoflurane, has been suggested. The TWIK-related K+ channel-1 (TREK-1) controls several major cellular responses involved in memory formation and is believed to participate in the development of depression, cerebral ischemia and blood-brain barrier dysfunction. However, the specific role of TREK-1 in mediating anesthesia-induced POCD remains unknown. In the current study, we determined that exposure to isoflurane affected memory in middle-aged mice and altered TREK-1 expression. In addition, TREK-1 over-expression exacerbated isoflurane-induced memory impairment, while TREK-1 silence attenuated the impairment. Taken together, our data demonstrate that inhibition of TREK-1 protects mice from cognitive impairment induced by anesthesia and TREK-1 is a potential therapeutic target against memory impairment induced by volatile anesthetics.