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Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation [RNA-seq]

ABSTRACT: Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation [RNA-seq]

PROVIDER: PRJNA860786 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20339700_1.fastq.gz	Fastqsanger.gz
	SRR20339700_2.fastq.gz	Fastqsanger.gz
	SRR20339701_1.fastq.gz	Fastqsanger.gz
	SRR20339701_2.fastq.gz	Fastqsanger.gz
	SRR20339702_1.fastq.gz	Fastqsanger.gz

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Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation

Project description:Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation

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Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation [CUT&RUN]

Project description:Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation [CUT&RUN]

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Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation [RNA-seq]

Project description:Aerobic exercise is well known to promote neuroplasticity and hippocampal memory. In the developing brain, early-life exercise (ELE) can lead to lasting improvements in hippocampal function, yet molecular mechanisms underlying this phenomenon have not been fully explored. In this study, adolescent transgenic mice harboring the “NuTRAP” (Nuclear tagging and Translating Ribosome Affinity Purification) cassette in Emx1 expressing neurons (“Emx1-NuTRAP” mice) undergo ELE followed by a hippocampal learning task, in order to determine the molecular underpinnings of exercise contributing to improved hippocampal memory performance. We simultaneously isolate and sequence translating mRNA and nuclear chromatin from a single hippocampus in a cell-type specific manner (excitatory neurons), demonstrate validity of our new technical approach, and couple multi-omics sequencing data to evaluate histone modifications H4K8ac and H3K27me3 and their influence on gene expression after ELE. We then evaluate new gene expression – histone modification relationships specifically during hippocampal memory consolidation that may play a critical role in facilitated memory after ELE. Our data reveal novel candidate gene-histone modification interactions and implicate gene regulatory pathways involved in ELE’s impact on hippocampal learning and memory.

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Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation [CUT&RUN]

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Early-life exercise primes the murine neural epigenome to facilitate gene expression and hippocampal memory consolidation.

Project description:Aerobic exercise is well known to promote neuroplasticity and hippocampal memory. In the developing brain, early-life exercise (ELE) can lead to persistent improvements in hippocampal function, yet molecular mechanisms underlying this phenomenon have not been fully explored. In this study, transgenic mice harboring the "NuTRAP" (Nuclear tagging and Translating Ribosome Affinity Purification) cassette in Emx1 expressing neurons ("Emx1-NuTRAP" mice) undergo ELE during adolescence. We then simultaneously isolate and sequence translating mRNA and nuclear chromatin from single hippocampal homogenates containing Emx1-expressing neurons. This approach allowed us to couple translatomic with epigenomic sequencing data to evaluate the influence of histone modifications H4K8ac and H3K27me3 on translating mRNA after ELE. A subset of ELE mice underwent a hippocampal learning task to determine the gene expression and epigenetic underpinnings of ELE's contribution to improved hippocampal memory performance. From this experiment, we discover gene expression - histone modification relationships that may play a critical role in facilitated memory after ELE. Our data reveal candidate gene-histone modification interactions and implicate gene regulatory pathways involved in ELE's impact on hippocampal memory.

| S-EPMC9825372 | biostudies-literature

Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-18 | GSE208715 | GEO

Hippocampal expression data from FTY720- and vehicle-treated SCID mice following fear consolidation testing

Project description:FTY720/Fingolimod, an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. Here we show that FTY720 enters the nucleus where it is phosphorylated by sphingosine kinase 2 (SphK2) and nuclear FTY720-P that accumulates there, binds and inhibits class I histone deacetylases (HDACs) enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in various brain regions, including hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning leading to improvement of memory impairment independently of its immunosuppressive actions. Our data suggest that sphingosine-1-phosphate and SphK2 play specific roles in memory functions and that FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories. Microarrays were used to survey the effect of FTY720 treatment during contextual fear conditioning on hippocampal gene expression. Total RNA was isolated from individual hippocampi of SCID mice 1 hour following fear consolidation testing after the third day of FTY720 or saline treatment. Eight arrays were run in total: 4 FTY720-treated mice and 4 saline-treated control mice.

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