title: Electroacupuncture improves cognitive ability following cerebral ischemia reperfusion injury via CaM-CaMKIV-CREB signaling in the rat hippocampus.
abstract: The aim of the present study was to investigate the effect of electroacupuncture (EA) on cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via the calmodulin (CaM)-calmodulin-dependent protein kinase type IV (CaMKIV)-cyclic adenosine monophosphate response elements binding protein (CREB) intracellular signaling pathway in the hippocampus. In total, 45 adult female Sprague-Dawley rats were randomly divided into three groups, namely the sham group, the middle cerebral artery occlusion (MCAO) group and the MCAO + EA group. Rats in the MCAO and MCAO + EA groups were modeled for post-stroke cognitive impairment. EA was performed at the Baihui and Shenting acupuncture points for 30 min/day for one week in the MCAO + EA group. Behavioral testing was analyzed using a step-down apparatus, while 2,3,5-triphenyl tetrazolium chloride was used to detect the infarct volume and lesion size. In addition, CaM activity was assessed by cyclic nucleotide-dependent phosphodiesterase analysis, and the protein expression levels of CaM, CaMKIV, phosphorylated (p)-CaMKIV, CREB and p-CREB were analyzed by western blot analysis. The cerebral I/R injured rat model in the MCAO group was established successfully with regard to the infarct volume and neuronal lesion size, as compared with the sham group. EA was demonstrated to effectively improve the cognitive ability, as measured by the step-down apparatus test, and decrease the infarct volume when compared with the MCAO group (P<0.05). The step-down apparatus test for the EA-treated rats revealed improved learning and reduced memory impairment when compared with the MCAO group. Furthermore, CaM activity and CaM protein expression levels in the MCAO + EA group were lower compared with those in the MCAO group (P<0.05). By contrast, the protein expression levels of CaMKIV, p-CaMKIV, CREB and p-CREB were significantly reduced in the MCAO group when compared with the sham group (P<0.05), although the expression levels increased following EA treatment when compared with the MCAO group (P<0.05). Therefore, cognitive repair benefited from EA, and the main intracellular signaling pathway in the hippocampus was mediated by CaM-CaMKIV-CREB. EA effectively inhibited the expression and activity of CaM, while further enhancing the expression of CaMKIV and CREB, and their associated phosphorylated functions.
authors.affiliation: College of Rehabilitation Medicine, Fujian University of Traditional Medicine, Fuzhou, Fujian 350122, P.R. China; The Clinical Medicine Department, Fujian Health College, Fuzhou, Fujian 350101, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Rehabilitation Medicine, Fujian University of Traditional Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Ruhui
authors.initials: R
authors.lastname: Lin
authors.affiliation: College of Rehabilitation Medicine, Fujian University of Traditional Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.affiliation: Fujian Key Laboratory of Exercise Rehabilitation, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Yunan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Traditional Chinese Medicine Rehabilitation Research Center, State Administration of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Traditional Chinese Medicine Rehabilitation Research Center, State Administration of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Kunqiang
authors.initials: K
authors.lastname: Yu
authors.affiliation: Traditional Chinese Medicine Rehabilitation Research Center, State Administration of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jixiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Fujian Key Laboratory of Exercise Rehabilitation, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Li
authors.affiliation: Fujian Key Laboratory of Exercise Rehabilitation, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Li-Dian
authors.initials: LD
authors.lastname: Chen
keywords: calmodulin; calmodulin-dependent protein kinase type IV; cerebral ischemia-reperfusion; cognitive deficits; cyclic adenosine monophosphate response elements binding protein; electroacupuncture; hippocampus