Relationship Between mTOR Signaling Activation and Postoperative Neurocognitive Disorder in Aged Rats

Although incidence rates of postoperative neurocognitive disorder (PND) in aged individuals following noncardiac major surgery are rising as individuals are living longer, the mechanism of PND remains poorly understood. We wondered if mammalian target of rapamycin (mTOR) signaling might be associated with PND since mTOR controls some essential intracellular events.

To investigate whether surgery activates the mTOR signaling pathway in aged rats, leading to PND, and whether the mTOR inhibitor, rapamycin, can be used to alleviate PND.

We randomly assigned aged rats to four groups: normal control (C), isoflurane (I), surgery (S), and rapamycin (R). Then, we anesthetized Groups I, S, and R, following which, Groups S and R underwent a splenectomy. After surgery, Group R was administered rapamycin. We used the Morris water maze to test the rats' spatial learning and memory after surgery.

In Group S, escape latency (ie, the time to find the platform) was markedly higher, and the ratio of swimming time in the target quadrant was lower, compared to the other groups. In Group R, escape latency was markedly lower as compared with Group S, and the ratio of swimming time in the target quadrant was higher.

Our results indicate that an altered mTOR signaling pathway after a splenectomy causes PND in aged rats, which can be alleviated by rapamycin.