Electroacupuncture Ameliorates Learning and Memory and Improves Synaptic Plasticity via Activation of the PKA/CREB Signaling Pathway in Cerebral Hypoperfusion

Abstract

Electroacupuncture (EA) has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are ill-understood. The present study was undertaken to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following EA and to investigate the role of PKA/CREB pathway. We used a rat 2-vessel occlusion (2VO) model and delivered EA at Baihui (GV20) and Dazhui (GV14) acupoints. Morris water maze (MWM) task, electrophysiological recording, Golgi silver stain, Nissl stain, Western blot, and real-time PCR were employed. EA significantly (1) ameliorated the spatial learning and memory deficits, (2) alleviated long-term potentiation (LTP) impairment and the reduction of dendritic spine density, (3) suppressed the decline of phospho-CREB (pCREB) protein, brain-derived neurotrophic factor (BDNF) protein, and microRNA132 (miR132), and (4) reduced the increase of p250GAP protein of 2VO rats. These changes were partially blocked by a selective protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89), suggesting that the PKA/CREB pathway is potentially involved in the effects of EA. Moreover, any significant damage to the pyramidal cell layer of CA1 subregion was absent. These results demonstrated that EA could ameliorate learning and memory deficits and alleviate hippocampal synaptic plasticity impairment of cerebral hypoperfusion rats, potentially mediated by PKA/CREB signaling pathway.

RETRACTED ARTICLE: Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia

“…The PKA-CREB signaling pathway has also been previously emphasized upon due to its critical role in the process of memory acquisition (Vitolo et al, 2002 ). Interestingly, a previous study revealed that the PKA-CREB signaling pathway inhibitor could act to eliminate the beneficial effects of electroacupuncture on learning and memory (Zheng et al, 2016 ), which was largely consistent with the results observed in the present study, in which silencing CREB1 or inhibiting the PKA-CREB signaling pathway was suggested to promote apoptosis, aggravate cognitive dysfunction and suppress hippocampal cell proliferation.…”

“…Studies have previously revealed that in the event that the PKA/CREB signaling pathway was to be inhibited, individuals would display learning and memory deficits similar to that of patients suffering from AD (Chen et al, 2012 ). Based on the aforementioned literature, we are of the belief that CREB1 and the PKA/CREB signaling pathway are both involved in cognitive function, including that of the processes of memory formation and behavioral changes (Zheng et al, 2016 ; Cheng et al, 2015 ). Hence, the central objective of the present study was to elucidate the relationship of the CREB1 gene, the PKA-CREB signaling pathway and VD, in an attempt to form a basis in the search for a new treatment method for patients suffering from VD.…”

Therapeutic Effects of Wenxin Keli in Cardiovascular Diseases: An Experimental and Mechanism Overview

“…WXKL exhibited its anti-inflammation property by lowering the level of IL-6, tumor necrosis factor-α (TNF-α) and high sensitivity C-reactive protein (hs-CRP) ( Cao et al, 2016 ). In addition, WXKL could downregulate inflammatory related gene expression, such as chemokine receptor 1 (CX3CR1), mannose receptor ctype1 (MRC1), and formyl peptide receptor 1 (FPR1) ( Zheng et al, 2016 ), as shown in Figure 2A .…”

“…In addition, there was a large number of myocardial apoptotic nuclei and the apoptosis rates were significantly increased after the coronary artery occlusion surgery. WXKL effectively restored the LVEF and left ventricular fractional shortening (LVFS), improved left ventricular end-diastolic dimension (LViDd) and left ventricular end-systolic dimension (LViDs), reduced MI size and apoptosis rate ( Zeng et al, 2006 ; Liu et al, 2012 ; Guo et al, 2013 ; Wu et al, 2013 , 2017a , b ; Xing et al, 2013 ; Wang and Liu, 2014 ; Zheng et al, 2016 ; Jiang et al, 2017 ). And WXKL also could downregulate genes associated with apoptosis, such as cathepsin C (CTSC), tetratricopeptide repeat domain 5 (TTC5), and upregulated angiogenesis promoting genes such as R-spondin 3 (RSPO3) ( Zheng et al, 2016 ).…”

Electroacupuncture ameliorates motor dysfunction via inhibiting p66Shc-mediated oxidative stress and endoplasmic reticulum stress in rats with spinal cord injury

“…The GV14 is the con uence of Governor Vessel and the hand and foot three Yang meridians. Acupuncture stimulation of GV14 is believed to activate channel-Qi and involved in the improvement of headache, dizziness, insomnia, forgetfulness, cerebral thrombosis as well as cerebral infarction [28][29][30]. The GV4 is recognized the root of Yuan-Qi and the gateway of human body that implicates in adjustment of collaterals and strengthens the spine and kidneys functions [31,32].…”