Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

Yu Zhao,Xiaoling Zhu,Ertao He,Lize Xiong,Qiang Wang,Jianming Pei,Xiyao Chen,Lei Ma,Shaoyang Chen,Zhiyi Zuo,Zhenghua Zhu,Lihong Hou,Lixian Xu

doi:10.1186/1471-2202-13-111

Yu Zhao, Xiaoling Zhu + Show 11 more

Open Access

https://doi.org/10.1186/1471-2202-13-111

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Abstract

BackgroundElectroacupuncture (EA) pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling.ResultsEA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment.ConclusionsEA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

Highlights

Electroacupuncture (EA) pretreatment can induce the tolerance against focal cerebral ischemia
EA pretreatment significantly increased Notch1, Notch4 and Jag1 mRNA in the striatum before ischemia Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis for Notch1, Notch4, Jag1 and Hes1 genes, which are major Notch pathway components in the central nervous system, in striatum and hippocampus before middle cerebral arterial occlusion (MCAO) showed that the Notch1, Notch4 and Jag1 mRNA in striatum in EA group was up-regulated compared with Control group (CON) group
There were no significant differences between EA and CON groups in the mRNA level of the above genes in hippocampus (Figure 1B)

Summary

Introduction

Electroacupuncture (EA) pretreatment can induce the tolerance against focal cerebral ischemia. We tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Binding of Notch to its ligands, such as Jagged and Delta-like, results in two-step proteolytic cleavages of Notch receptor. The second cleavage accomplished by presenilin-1 and γ-secretase enzyme complex releases Notch intracellular domain (NICD) that translocates to the nucleus where it regulates transcription of the Notch target genes, such as Hes family. This process is the canonical Notch signaling [1,2]. Notch signaling is implicated in neural development, including the maintenance of self-renewal potential in stem cells, binary cell-fate determination in progenitor cells and induction of terminal differentiation

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