MicroRNA involvement in mechanism of endogenous protection induced by fastigial nucleus stimulation based on deep sequencing and bioinformatics.

Ling-Bo Feng,Xia Zhou,Hui-Yao Xiang,Jin-Pin Li,Lei Zhang,Chun-Yong Chen,Sheng-You Su,Sheng-Hua Li,Jing-Li Liu,Xiao-Min Pang,Li-Gang Huang

doi:10.1186/s12920-015-0155-4

Abstract

BackgroundNeurogenic neuroprotection is a promising approach for treating patients with ischemic brain lesions. Fastigial nucleus stimulation (FNS) has been shown to reduce the tissue damage resulting from focal cerebral ischemia in the earlier studies. However, the mechanisms of neuroprotection induced by FNS remain unclear. MicroRNAs (miRNAs) are a newly discovered group of non-coding small RNA molecules that negatively regulate target gene expression and involved in the regulation of pathological process. To date, there is a lack of knowledge on the expression of miRNA in response to FNS. Thus, we study the regulation of miRNAs in the rat ischemic brain by the neuroprotection effect of FNS.MethodsIn this study, we used an established focal cerebral ischemia/reperfusion (IR) model in rats. MiRNA expression profile of rat ischemic cortex after 1 h of FNS were investigated using deep sequencing. Microarray was performed to study the expression pattern of miRNAs. Functional annotation on the miRNA was carried out by bioinformatics analysis.ResultsTwo thousand four hundred ninety three miRNAs were detected and found to be miRNAs or miRNA candidates using deep sequencing technology. We found that the FNS-related miRNAs were differentially expressed according microarray data. Bioinformatics analysis indicated that several differentially expressed miRNAs might be a central node of neuroprotection-associated genetic networks and contribute to neuroprotection induced by FNS.ConclusionsMiRNA acts as a novel regulator and contributes to FNS-induced neuroprotection. Our study provides a better understanding of neuroprotection induced by FNS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0155-4) contains supplementary material, which is available to authorized users.

Highlights

Neurogenic neuroprotection is a promising approach for treating patients with ischemic brain lesions
Electrical stimulation of the fastigial nucleus (FN) and transient focal cerebral ischemia Rats were anesthetized with an intraperitoneal injection of 3.5 % chloral hydrate (1.0 ml/100 g, Sigma, Missouri, USA)
Analysis and annotation of sequencing data A cDNA library of small RNAs was prepared from a mixture of rat ischemic cortex tissue at 5 time points (3 h, 6 h, 12 h, 24 h and 72 h) of reperfusion after 1 h of Fastigial nucleus stimulation (FNS)

Summary

Introduction

Neurogenic neuroprotection is a promising approach for treating patients with ischemic brain lesions. Fastigial nucleus stimulation (FNS) provides long-lasting protection against ischemic infarction, which is emerging as one of promising approaches for treating patients with ischemic brain lesions [4]. MicroRNAs (miRNAs), a large family of ~22 nucleotide (nt) single-stranded non-coding small RNAs, are derived from ~70 nt long stem-loop precursors (premiRNAs) [14, 15]. They are found in various species of animals, plants and viruses. Studies have suggested that miRNA may be an inducible factor to response on the neuroprotection of ischemic pre-conditioning (IPC) through their function in regulating gene expression [21, 22]. Whether FN stimulation exerts its effect through miRNAs regulation mechanisms remains unclear

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Conclusion