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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 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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The clock gene Per1 may exert diurnal control over hippocampal memory consolidation

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FOXO1-KLF10 reinforcing loop promotes adipose lipolysis to facilitate exercise-induced anti-obesity effect in male mice

Project description:Exercise is recognized to be an effective way in the combat against obesity and related metabolic disorders, but the underlying mechanism is incompletely understood. Krüppel-like factor 10 (KLF10) is a transcription factor participating in diverse biological processes. KLF10 expression is abundant in adipose tissue, but its role in obesity is not well defined. Here, we show that exercise could facilitate adipocyte-derived KLF10 expression via the SIRT1/FOXO1 pathway. Adipocyte-specific knockout of KLF10 (KLF10AKO) blunts exercise-promoted white adipose browning, energy expenditure, fat loss, and glucose tolerance in diet-induced obese (DIO) mice. On the contrary, adipocyte-specific transgenic expression of KLF10 in mice (KLF10ATG) enhanced the abovementioned metabolic benefits induced by exercise. Mechanistically, KLF10 interacts with FOXO1 and facilitates the recruitment of KDM4A to form a ternary complex on the promoter regions of the Pnpla2 and Lipe genes to promote the expression of these key lipolytic genes, therefore facilitating lipolysis to defend against DIO in mice. As a newfound downstream effector responding to exercise, adipose KLF10 could act as a potential target in the fight against obesity

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