Physical exercise shapes the mouse brain epigenome.

Area of Science:

• Neuroscience
• Epigenetics
• Genomics

Background:

• Exercise, including endurance and resistance training, is known to benefit brain health.
• The specific molecular mechanisms underlying these benefits, particularly at the epigenomic and transcriptomic levels in the hippocampus, remain incompletely understood.

Purpose of the Study:

• To investigate the genome-wide epigenomic and transcriptomic alterations in the mouse hippocampus following long-term resistance or endurance training.
• To assess the impact of these training interventions on cognitive function, specifically learning and memory.

Main Methods:

• Whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) were performed on mouse hippocampi after 4 weeks of training.
• A novel object recognition test was employed to evaluate cognitive performance before and after the exercise intervention.

Main Results:

• Most DNA methylation changes were training-model specific, predominantly showing hypomethylation and enrichment in specific histone marks and transcription factor binding sites.
• Loss of DNA methylation at Tet1 binding sites correlated significantly with gene expression changes, highlighting its role in transcriptional regulation.
• Endurance exercise activated neuroplasticity pathways, while resistance exercise engaged interferon response pathways, both associated with enhanced learning and memory.

Conclusions:

• The study elucidates distinct molecular mechanisms by which different exercise modalities impact brain health.
• Findings provide potential therapeutic targets for future research aimed at enhancing cognitive function and brain health through exercise-related interventions.