Genome-wide identification of brain miRNAs in response to high-intensity intermittent swimming training in Rattus norvegicus by deep sequencing

Yanhong Zhao,Yanfang Wang,Anmin Zhang,Shuping Hu,Shuaiwei Qian,Ruiping Zhang

doi:10.1186/s12867-019-0120-4

Abstract

BackgroundPhysical exercise can improve brain function by altering brain gene expression. The expression mechanisms underlying the brain’s response to exercise still remain unknown. miRNAs as vital regulators of gene expression may be involved in regulation of brain genes in response to exercise. However, as yet, very little is known about exercise-responsive miRNAs in brain.ResultsWe constructed two comparative small RNA libraries of rat brain from a high-intensity intermittent swimming training (HIST) group and a normal control (NC) group. Using deep sequencing and bioinformatics analysis, we identified 2109 (1700 from HIST, 1691 from NC) known and 55 (50 from HIST, 28 from NC) novel candidate miRNAs. Among them, 34 miRNAs were identified as significantly differentially expressed in response to HIST, 16 were up-regulated and 18 were down-regulated. The results showed that all members of mir-200 family were strongly up-regulated, implying mir-200 family may play very important roles in HIST response mechanisms of rat brain. A total of 955 potential target genes of these 34 exercise-responsive miRNAs were identified from rat genes. Most of them are directly involved in the development and regulatory function of brain or nerve. Many acknowledged exercise-responsive brain genes such as Bdnf, Igf-1, Vgf, Ngf c-Fos, and Ntf3 etc. could be targeted by exercise-responsive miRNAs. Moreover, qRT-PCR and SABC immunohistochemical analysis further confirm the reliability of the expression of miRNAs and their targets.ConclusionsThis study demonstrated that physical exercise could induce differential expression of rat brain miRNAs and 34 exercise-responsive miRNAs were identified in rat brain. Our results suggested that exercise-responsive miRNAs could play important roles in regulating gene expression of rat brain in response to exercise.

Highlights

Physical exercise can improve brain function by altering brain gene expression
The expression level of brain-derived neurotrophic factor (BDNF) gene in various brain regions can be significantly increased after exercise [1, 14, 15], which is one of the major factors affecting on neuronal survival and differentiation as well as synaptic plasticity
Deep sequencing read analysis Deep sequencing yielded a total of 28,667,031 high-intensity intermittent swimming training (HIST) and 21,372,487 normal control (NC) raw reads from HIST and NC libraries, respectively (Table 1)

Summary

Introduction

Physical exercise can improve brain function by altering brain gene expression. The expression mechanisms underlying the brain’s response to exercise still remain unknown. miRNAs as vital regulators of gene expression may be involved in regulation of brain genes in response to exercise. Many studies using animal models have demonstrated that physical exercise leads to differential expression of the brain genes encoding c-FOS [18, 19], NMDAR1 [20], VEGF [21, 22], Flk-1 [20], NT-3 [23], and VGF [24] etc. Such expression changes may contribute significantly to the beneficial effects of exercise [13]. It is still not clear how physical exercise alters gene expression profiling in brain

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