Background: Electroacupuncture (EA) has been shown to reduce cognitive impairment in vascular dementia (VaD) patients. However, the mechanism of action remains unknown. Objective: The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in apoptosis. Herein, we focused on whether EA can inhibit apoptosis and alleviate cognitive impairment by regulating the JNK signaling pathway using a mouse model of VaD induced by modified bilateral common carotid artery occlusion (BCCAo). Methods: In experiment I, 60 mice were randomly divided into a Sham group, BCCAo group, BCCAo + EA group, BCCAo + Sham-EA group, BCCAo + SP group (receiving the selective JNK inhibitor SP600125) and BCCAo + SP + EA group. Morris water maze tests, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining and flow cytometry were used to evaluate the effect of the EA intervention on VaD. In experiment II, 30 mice were randomly divided into a Sham group, BCCAo group, BCCAo + EA group, BCCAo + SP group and BCCAo + SP + EA group. Western blotting and real-time reverse transcription polymerase chain reaction were used to detect protein and mRNA expression of key factors in the JNK signaling pathway in the hippocampus. Results: EA, SP600125 and EA + SP600125 significantly inhibited hippocampal apoptosis and improved cognitive impairment in VaD model mice. There were no significant differences between the BCCAo group and the BCCAo + Sham-EA group. EA, EA + SP600125 and SP600125 inhibited the phosphorylation of JNK and caspase-3. EA and EA + SP600125 promoted protein and mRNA expression of B-cell lymphoma 2 (Bcl-2) in the hippocampus of VaD mice and inhibited protein and mRNA expression of activator protein (AP)-1, p53 and Bax. Conclusion: EA can reverse cognitive deficits and inhibit hippocampal neuronal apoptosis in VaD model mice, at least partially through inhibition of the JNK signaling pathway and regulation of apoptosis signals.
Background: Nerve cell apoptosis is an important pathological mechanism of vascular dementia (VaD). There are evidences that Electroacupuncture (EA) can reduce cognitive impairment in VaD patients and protect nerve cells. However, the mechanism remains unknown. JNK signaling pathway play an important role in apoptosis. And JNK induces cell apoptosis in two main ways, namely JNK transcription-dependent pathway and JNK transcription-independent route. We focus on whether EA can inhibit apoptosis and alleviate cognitive impairment by regulating JNK signaling pathway.Method: In this study, Bilateral common carotid artery clipping (BCCAo) was used as a method to establish VaD mouse model. Longa scoring method and Morris water maze were used to evaluate whether EA could improve the behavioral score of VaD mice. The neuroprotective effects of EA were evaluated by the Hematoxylin and Eosin (HE) staining, TUNEL and Flow Cytometry (FCM). Western blot and real-time PCR were used to detect the expression of JNK-3, AP-1, P53, Bcl -2, Bax, and Caspase-3.Results: Our findings indicated that EA could improve the behavioral scores of VaD mice. VaD mice treated with EA reduced hippocampal neuronal apoptosis. In addition, EA could reduce the expression of JNK-3, AP-1, P53, Bax and Caspase-3 proteins and mRNA in the hippocampus of VaD mice, and increase the expression of Bcl-2.Conclusion: Our findings suggested that the mechanism of action of EA to treat VaD may be related to its regulation of JNK transcription-dependent pathway and JNK transcription-independent route.
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