Jansen Fernandes1, Andre Schwambach Vieira2, Juliana Carlota Kramer-Soares3, Eduardo Alves Da Silva1, Kil Sun Lee4, Iscia Lopes-Cendes5, Ricardo Mario Arida6. 1. Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. 2. Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil. 3. Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. 4. Department of Biochemistry, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. 5. Department of Medical Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. 6. Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: arida.nexp@epm.br.
Abstract
BACKGROUND: It is widely known that physical activity positively affects the overall health and brain function. Recently, microRNAs (miRNAs) have emerged as potential regulators of numerous biological processes within the brain. These molecules modulate gene expression post-transcriptionally by inducing mRNA degradation and inhibiting the translation of target mRNAs. METHODS: To verify whether the procognitive effects of physical exercise are accompanied by changes in the activity of miRNA-mRNA network in the brain, differential expression analysis was performed in the hippocampus of control (CTL) and exercised (Ex) rats subjected to 4 weeks of treadmill exercise. Cognition was evaluated by a multiple trial inhibitory avoidance (MTIA) task and Illumina next-generation sequencing (NGS) was used for miRNA and mRNA profiling. RESULTS: Exercise improved memory retention but not acquisition in the MTIA task. It was observed that 4 miRNAs and 54 mRNAs were significantly altered in the hippocampus of Ex2 (euthanized 2 h after the last exercise bout) group when compared to CTL group. Bioinformatic analysis showed an inverse correlation between 3 miRNAs and 6 target mRNAs. The miRNAs miR-129-1-3p and miR-144-5p were inversely correlated to the Igfbp5 and Itm2a, respectively, and the miR-708-5p presented an inverse correlation with Cdkn1a, Per2, Rt1-a2. CONCLUSION: The exercise-induced memory improvements are accompanied by changes in hippocampal miRNA-mRNA regulatory network. GENERAL SIGNIFICANCE: Physical exercise can affect brain function through modulation of epigenetics mechanisms involving miRNA regulation.
BACKGROUND: It is widely known that physical activity positively affects the overall health and brain function. Recently, microRNAs (miRNAs) have emerged as potential regulators of numerous biological processes within the brain. These molecules modulate gene expression post-transcriptionally by inducing mRNA degradation and inhibiting the translation of target mRNAs. METHODS: To verify whether the procognitive effects of physical exercise are accompanied by changes in the activity of miRNA-mRNA network in the brain, differential expression analysis was performed in the hippocampus of control (CTL) and exercised (Ex) rats subjected to 4 weeks of treadmill exercise. Cognition was evaluated by a multiple trial inhibitory avoidance (MTIA) task and Illumina next-generation sequencing (NGS) was used for miRNA and mRNA profiling. RESULTS: Exercise improved memory retention but not acquisition in the MTIA task. It was observed that 4 miRNAs and 54 mRNAs were significantly altered in the hippocampus of Ex2 (euthanized 2 h after the last exercise bout) group when compared to CTL group. Bioinformatic analysis showed an inverse correlation between 3 miRNAs and 6 target mRNAs. The miRNAs miR-129-1-3p and miR-144-5p were inversely correlated to the Igfbp5 and Itm2a, respectively, and the miR-708-5p presented an inverse correlation with Cdkn1a, Per2, Rt1-a2. CONCLUSION: The exercise-induced memory improvements are accompanied by changes in hippocampal miRNA-mRNA regulatory network. GENERAL SIGNIFICANCE: Physical exercise can affect brain function through modulation of epigenetics mechanisms involving miRNA regulation.
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