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Silencing of exercise induced microRNA-501, microRNA-409 leads to aberrant neuronal homeostasis

ABSTRACT: Silencing of exercise induced microRNA-501, microRNA-409 leads to aberrant neuronal homeostasis

PROVIDER: PRJNA720378 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14163417.fastq.gz	Fastqsanger.gz
	SRR14163418.fastq.gz	Fastqsanger.gz
	SRR14163419.fastq.gz	Fastqsanger.gz
	SRR14163420.fastq.gz	Fastqsanger.gz
	SRR14163421.fastq.gz	Fastqsanger.gz

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Silencing of exercise induced microRNA-501, microRNA-409 leads to aberrant neuronal homeostasis

Project description:Exercise has been shown to boost cognition in mammals. However, the underlying mechanism remain poorly understood. We hypothesized that circulating microRNAs may correlate to improved cognitive functions, particularly cognitive flexibility after exercise and could be critical for neurons functions. To address this, in our study, healthy human volunteers participated in an exercise paradigm coupled with various cognitive tests performed prior to and after exercise and high quality small RNAome data were generated from total blood collected at two time points (pre- and post-exercise). Advanced comparative computational approaches were employed to select candidate microRNAs and multiple functional experiments were designed to test effect of those candidates on neuronal transcriptome, and neuronal functions. Our analyses revealed a cluster of circulating microRNAs related to improved cognitive flexibility. After rigorous analyses, we selected two candidate microRNAs and inhibition of these microRNAs led to up-regulation of genes, conserved in increased stress responses and downregulation of genes related to synaptic morphology and functions. Functional data revealed that the two microRNAs are indeed critical for maintenance of neuronal functions and morphology. Newly discovered cluster of microRNAs shed light on the mechanism of exercise-improved cognition and the two candidate microRNAs are potential RNA therapeutic target against dementia.

2022-04-07 | GSE171633 | GEO

Exercise as a model to identify microRNAs linked to human cognition: a role for microRNA-409 and microRNA-501.

Project description:MicroRNAs have been linked to synaptic plasticity and memory function and are emerging as potential biomarkers and therapeutic targets for cognitive diseases. Most of these data stem from the analysis of model systems or postmortem tissue from patients which mainly represents an advanced stage of pathology. Due to the in-accessibility of human brain tissue upon experimental manipulation, it is still challenging to identify microRNAs relevant to human cognition, which is however a key step for future translational studies. Here, we employ exercise as an experimental model for memory enhancement in healthy humans with the aim to identify microRNAs linked to memory function. By analyzing the circulating smallRNAome we find a cluster of 18 microRNAs that are highly correlated to cognition. MicroRNA-409-5p and microRNA-501-3p were the most significantly regulated candidates. Functional analysis revealed that the two microRNAs are important for neuronal integrity, synaptic plasticity, and morphology. In conclusion, we provide a novel approach to identify microRNAs linked to human memory function.

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Effects of exercise on microRNA expression level in human monocytes

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A myogenin+/CD74+ adult muscle stem cell population during regeneration of skeletal muscle lacking miR-501

Project description:Adult muscle stem cells show a high transcriptional and clonal heterogeneity during ageing. Whether microRNAs contribute to this diversity is not known. Here we use tissue-specific genetic deletion of microRNA (miR)-501 that is highly enriched in activated myogenic progenitor cells to address this question. Single-cell sequencing revealed a novel subpopulation of committed myogenic progenitor cells in miR-501 knockout mice that express high levels of terminal differentiation markers and inflammatory genes such as CD74. Our data show that stem cell heterogeneity in skeletal muscle during ageing is under miRNA control.

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microRNA data from high-fat diet fed mice with and without exercise

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Sinorhizobium meliloti strain:409

Project description:Sinorhizobium meliloti 409 Resequencing

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RNA sequencing of TA muscle in miR-501KO mice and control littermates at day 6 of CTX-induced muscle regeneration

Project description:Adult muscle stem cells show a high transcriptional and clonal heterogeneity during ageing. Whether microRNAs contribute to this diversity is not known. Here we use global and tissue-specific genetic deletion of microRNA (miR)-501 that is highly enriched in activated myogenic progenitor cells 3 to address this question. Deletion of miR-501 reduced myofiber size and resilience of muscle fibers to injury and exercise in adult skeletal muscle. miR-501 elicits this effect by changing sarcomeric gene expression in newly built myofibers in vivo.

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Project description:Exercise leads to a rapid change in the profile of gene expression in monocytes. We hypothesized that microRNA expression in circulating monocytes would also be affected by brief exercise. Twelve healthy men (22-30yr old) performed 10 2-min bouts of cycle ergometer exercise interspersed with 1-min rest at a constant work equivalent to about82% of VO2max. A baseline blood sample was taken before the and immediately after the exercise. Monocytes were isolated from PBMC using a negative magnetic cell separation methods (Miltenyi Biotec Monocyte Isolation Kit II, human #130-091-153 and the autoMACSM-BM-. Pro Separator). Total RNA was extracted using TRIzolM-BM-.. For this study we used Agilent Human miRNA microarrays V2 (total of 24 arrays).

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