Electroacupuncture Reduced Apoptosis of Hippocampal Neurons in Mice with Cerebral Infarction by Regulating the Notch3 Signaling Pathway
- 13 Downloads
This study is designed to explore the effect of electric acupuncture on the apoptosis of hippocampal neurons through the Notch3 signaling pathway. A middle cerebral artery occlusion (MCAO) mouse model was generated by thread embolization. A Y-maze was used to test cognitive function (learning and memory). The apoptosis factor caspase-3 was identified through an enzyme-linked immunosorbent assay (ELISA). TTC staining was used to evaluate the cerebral infarction area. Apoptosis of hippocampal neurons was identified by TUNEL staining and flow cytometry. The expression levels of genes and proteins related to the Notch3 signaling pathway were assessed by qRT-PCR and Western blot. It was determined that 7 days of electroacupuncture treatment improved recovery from cerebral infarction. Electroacupuncture therapy reduced the cerebral infarction area in mice and decreased the apoptosis of hippocampal neurons. The apoptosis rate of hippocampal neurons and the area of cerebral infarction were significantly lower in the electroacupuncture group than in the MCAO group (P < 0.01), while the apoptosis rate of hippocampal neurons and the area of cerebral infarction were significantly higher in the inhibitor group than in the electroacupuncture group (P < 0.01). The expression levels of genes related to the Notch3 signaling pathway were significantly increased in the electric acupuncture treatment group compared with the MCAO group (P < 0.01). The results showed that electroacupuncture inhibited the apoptosis of hippocampal neurons through the Notch3 signaling pathway, while the expression levels of genes related to the Notch3 signaling pathway were significantly higher in the inhibitor group than in the electroacupuncture group (P < 0.01). Electroacupuncture inhibited the apoptosis of hippocampal neurons in mice with cerebral infarction by stimulating the Notch3 signaling pathway and triggering corresponding protein expression.
KeywordsCerebral infarction Electric acupuncture Notch3 signaling pathway Hippocampal neuron
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine.
Informed consent was obtained from all individual participants included in the study.
- Campbell MT, Dagher P, Hile KL, Zhang H, Meldrum DR, Rink RC, Meldrum KK (2008) Tumor necrosis factor-alpha induces intrinsic apoptotic signaling during renal obstruction through truncated bid activation. J Urol 180:2694–2700. https://doi.org/10.1016/j.juro.2008.08.001 CrossRefPubMedPubMedCentralGoogle Scholar
- D'Angelo RC, Ouzounova M, Davis A, Choi D, Tchuenkam SM, Kim G, Luther T, Quraishi AA, Senbabaoglu Y, Conley SJ, Clouthier SG, Hassan KA, Wicha MS, Korkaya H (2015) Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity. Mol Cancer Ther 14:779–787. https://doi.org/10.1158/1535-7163.MCT-14-0228 CrossRefPubMedPubMedCentralGoogle Scholar
- Ding W, Chen R, Wu C, Chen W, Zhang H, Fan X, Wang H, Ji Y, Xie L, Ning X, Shen L (2017) Increased expression of HERPUD1 involves in neuronal apoptosis after intracerebral hemorrhage. Brain Res Bull 128:40–47. https://doi.org/10.1016/j.brainresbull.2016.11.006 CrossRefPubMedGoogle Scholar
- Du Y, Shi L, Li J, Xiong J, Li B, Fan X (2011) Angiogenesis and improved cerebral blood flow in the ischemic boundary area were detected after electroacupuncture treatment to rats with ischemic stroke. Neurol Res 33:101–107. https://doi.org/10.1179/016164110X12714125204317 CrossRefPubMedGoogle Scholar
- Liu J, Wang Q, Yang S, Huang J, Feng X, Peng J, Lin Z, Liu W, Tao J, Chen L (2018) Electroacupuncture inhibits apoptosis of peri-ischemic regions via modulating p38, extracellular signal-regulated kinase (ERK1/2), and c-Jun N terminal kinases (JNK) in cerebral ischemia-reperfusion-injured rats. Med Sci Monit 24:4395–4404. https://doi.org/10.12659/MSM.908473 CrossRefPubMedPubMedCentralGoogle Scholar
- Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Götz M, Haas CA, Kempermann G, Taylor V, Giachino C (2010) Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6:445–456. https://doi.org/10.1016/j.stem.2010.03.017 CrossRefPubMedGoogle Scholar
- Qi L, Han Z, Zhou Y, Chen W, Chu L, Lu J, Xu W, Wang H, Wang Z, Ling J (2018) Dynamic scalp acupuncture combined with PNF therapy for upper limb motor impairment in ischemic stroke spastic hemiplegia. Zhongguo Zhen Jiu 38:234–238. https://doi.org/10.13703/j.0255-2930.2018.03.002 CrossRefPubMedGoogle Scholar
- Wang Y, Wan C, Yu S, Yang L, Li B, Lu T, Bi Y, Jiang J, Cui G (2014b) Upregulated expression of NF-YC contributes to neuronal apoptosis via proapoptotic protein bim in rats’ brain hippocampus following middle cerebral artery occlusion (MCAO). J Mol Neurosci 52:552–565. https://doi.org/10.1007/s12031-013-0111-8 CrossRefPubMedGoogle Scholar
- Zhao Y, Chen X, Ma L, Zuo Z, Zhu Z, Zhu X, Wang Q, He E, Xiong L, Pei J, Xu L, Hou L, Chen S (2012) Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway. BMC Neurosci 13:111. https://doi.org/10.1186/1471-2202-13-111 CrossRefPubMedPubMedCentralGoogle Scholar
- Zhou Y, Tong D, Wang S, Liu L, Ye S, Xu B (2017a) Comparison of risk of death between older and non-older critical patients in ICU: a retrospective cohort study of consecutive 3 years. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 29:448–452. https://doi.org/10.3760/cma.j.issn.2095-4352.2017.05.012 CrossRefPubMedGoogle Scholar
- Zhuang Y, Xing JJ, Li J, Zeng BY, Liang FR (2013) History of acupuncture research. Int Rev Neurobiol 111:1–23. https://doi.org/10.1016/B978-0-12-411545-3.00001-8 CrossRefPubMedGoogle Scholar