Role of hippocampal AMPK signaling pathway in reduction of postoperative cognitive dysfunction by electroacupuncture preconditioning in aged rats

Abstract

Objective To evaluate the role of hippocampal adenosine monophosphate-activated protein kinase(AMPK)signaling pathway in reduction of postoperative cognitive dysfunction by electroacupuncture(EA)preconditioning in aged rats. Methods A total of 150 healthy male Sprague-Dawley rats, aged 18-20 months, weighing 400-500 g, were randomly divided into 5 groups(n=30 each)using a random number table: control group(group C); splenectomy group(group O); preconditioning with EA at non-acupoint group(group NEA); preconditioning with EA at Baihui acupoint group(group EA); preconditioning with EA at Baihui acupoint + AMPK inhibitor group(group EAC). EA and EAC groups received EA at Baihui acupoints with a sparse-dense wave at an intensity of 1 mA and a frequency of 2 Hz/15 Hz for 30 min, once a day, for 5 consecutive days, and splenectomy was performed at 24 h after the end of the last stimulation.Group NEA received EA at the points 2 mm lateral to the acupoints of Baihui, and the other treatments were similar to those previously described in group EA.Compound C 20 mg/kg was injected intraperitoneally at 5 min before operation in group EAC.Morris water maze test was performed at 1, 3 and 5 days after operation, and the escape latency and swimming distance were recorded.The rats were then sacrificed, and brains were removed for examination of the pathological changes in the hippocampal CA3 region and for determination of the expression of AMPK, phosphorylated AMPK(p-AMPK), nuclear factor kappa B(NF-κB), interleukin-1beta(IL-1β), and tumor necrosis factor-alpha(TNF-α)by Western blot. Results Compared with group C, the escape latency and swimming distance were significantly prolonged, and the expression of AMPK, p-AMPK, NF-κB, IL-1β, and TNF-α was significantly up-regulated in O, NEA, EA and EAC groups(P 0.05). Compared with group EA, the escape latency and swimming distance were significantly prolonged, the expression of AMPK and p-AMPK was significantly down-regulated, and the expression of NF-κB, IL-1β and TNF-α was significantly up-regulated in group EAC(P<0.05). Conclusion Activation of hippocampal AMPK signaling pathway is involved in EA preconditioning-induced improvement in postoperative cognitive dysfunction in aged rats. Key words: Protein-serine-threonine kinases; Signal transduction; Hippocampus; Electric stimulation therapy; Ischemic preconditioning; Cognition disorders; Aged