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Getting to Compliance in Forced Exercise in Rodents: A Critical Standard to Evaluate Exercise Impact in Aging-related Disorders and Disease
Published on: August 22, 2014
Multi-omics delineate growth factor network underlying exercise effects in an Alzheimer's mouse model
Xin Li1, Chaozhong Liu2,3,4, Wenbo Li1
1Department of Medicine, Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, Texas, USA.
Summary
Physical exercise combats cognitive decline by activating specific cell networks in the brain. Targeting epidermal growth factor receptor (EGFR) signaling enhances memory, offering a new strategy against Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Physical exercise is crucial for preventing age-related cognitive decline and Alzheimer's disease (AD).
- Understanding the molecular mechanisms behind exercise's neuroprotective effects is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the cell type-specific molecular changes in the hippocampus induced by exercise in a mouse model of Alzheimer's disease.
- To identify key signaling pathways, such as epidermal growth factor receptor (EGFR) signaling, involved in exercise-mediated cognitive benefits.
Main Methods:
- Single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) were performed on the hippocampus of APPNL-G-F mice.
- Mice underwent prolonged voluntary wheel-running exercise to assess the impact on gene expression and chromatin accessibility.
Main Results:
- Exercise counteracted amyloid-induced changes in the transcriptome and chromatin accessibility in a cell type-specific manner.
- These beneficial effects were mediated by regulatory networks converging on growth factor signaling, particularly EGFR and insulin signaling.
- Pharmacological inhibition of EGFR and PI3K blocked the cognitive enhancements from exercise.
- Intranasal administration of heparin-binding EGF (HB-EGF) improved memory in sedentary mice.
Conclusions:
- Exercise activates specific hippocampal transcriptional networks that promote memory enhancement.
- EGFR signaling is a key druggable target for harnessing exercise's benefits to combat Alzheimer's-related cognitive decline.
