The role of the PI3K/Akt/GSK-3β pathway in postoperative cognitive dysfunction in elderly rats

The goal of this study was to investigate the effect of anesthesia and surgery on postoperative cognitive dysfunction (POCD). The role of the PI3K/Akt/GSK-3 beta pathway in POCD in elderly rats was also studied using 22-month-old female Sprague Dawley (SD) rats that were randomly assigned into a sham group, a splenectomy group and an anesthesia group, with 10 rats in each group. Morris water maze training was performed 6 days prior to the animal model construction. After establishment of anesthesia and splenectomy animal models for 7 days, the reverse Morris water maze test was performed to compare the behavioral differences among the three groups. Vital signs of each rat were detected. Expression levels of relative genes in the PI3K/Akt/GSK-3 beta pathway were detected by Western blot and quantitative real time-polymerase chain reaction (qRT-PCR), respectively. Compared with the control group, the swimming distance and latency period were increased (P<0.05), whereas the target quadrant retention time ratio was decreased in anesthesia group and splenectomy group. No significant difference in swimming speed was seen among the three groups. qRT PCR results indicated that the mRNA levels of PI3K, AKT, and GSK-313 were decreased, whereas Cyto C and caspase-9 were increased in rat hippocampus of the anesthesia group and the splenectomy group (P<0.05). Downregulated p-PI3K, p-AKT, and GSK-3 beta, as well as upregulated Cyto-C and caspase-9 was found in the anesthesia group and splenectomy group by Western blot (P<0.05). Furthermore, no significant differences in the abovementioned gene expressions were found between the anesthesia group and splenectomy group (P>0.05). Anesthesia can cause cognitive dysfunction in elderly rats. There was no correlation between procedures and cognitive function decline. Inhibition of PI3K/Akt/GSK-3 beta pathway caused by anesthesia may lead to apoptosis of hippocampal tissue, which may be explained for the postoperative cognitive dysfunction.