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RNA-Sequencing of Running-dependent and Running-independent Environmental Enrichment in the Adult Mouse Dentate Gyrus

ABSTRACT: RNA-Sequencing of Running-dependent and Running-independent Environmental Enrichment in the Adult Mouse Dentate Gyrus

PROVIDER: PRJNA419888 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6323970_1.fastq.gz	Fastqsanger.gz
	SRR6323970_2.fastq.gz	Fastqsanger.gz
	SRR6323971_1.fastq.gz	Fastqsanger.gz
	SRR6323971_2.fastq.gz	Fastqsanger.gz
	SRR6323972_1.fastq.gz	Fastqsanger.gz

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RNA-Sequencing of Running-dependent and Running-independent Environmental Enrichment in the Adult Mouse Dentate Gyrus

Project description:We used RNA sequencing to perform an unbiased interrogation of DG gene expression in CD1 mice exposed to either a voluntary running disc (RUN), a running-independent complex environment (CE, containing a locked disc, social enrichment and tunnels), or a locked disc alone (LD). RNA sequencing revealed that both RUN and CE mice showed significant, and largely non-overlapping, transcriptomic differences versus the LD control. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses about novel mediators of EE-induced cognitive changes.

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Project description:To identify genes responsible for stem and progenitor cells maintenance, we sought here to find genes underlying premature neural aging, and whose deregulated expression could be rescued by running. Through RNA sequencing we analyzed the transcriptomic profiles of the dentate gyrus isolated from Btg1 wild-type or Btg1 knockout adult (two-month-old) mice submitted to physical exercise or sedentary. In Btg1 knockout mice, 545 genes were deregulated, relative to wild-type, while 2081 genes were deregulated by running. We identified 42 genes whose expression was not only down-regulated in the dentate gyrus of Btg1 knockout, but was also counter-regulated to control levels by running in Btg1 knockout mice, vs. sedentary.

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RNA-Sequencing Reveals Unique Transcriptional Signatures of Running and Running-Independent Environmental Enrichment in the Adult Mouse Dentate Gyrus.

Project description:Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running's genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

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