Long-term exercise modulates hippocampal gene expression in senescent female mice

Area of Science:

• Neuroscience
• Gerontology
• Molecular Biology

Background:

• The senescence-accelerated SAMP8 mouse model mimics aspects of cognitive decline and Alzheimer's disease (AD).
• Understanding the molecular mechanisms of brain aging and exercise intervention is crucial for developing strategies against age-related cognitive impairment.

Purpose of the Study:

• To investigate the effects of long-term voluntary wheel running on aging phenotypes and hippocampal gene expression in SAMP8 mice.
• To identify specific genes in the hippocampus that are altered by aging and responsive to physical exercise.

Main Methods:

• Six months of voluntary wheel running was administered to 10-month-old female SAMP8 mice, with SAMR1 mice serving as controls.
• Whole genome microarray analysis was performed on hippocampal tissue from sedentary SAMP8, sedentary SAMR1, and exercised SAMP8 mice.
• Gene ontology analysis and real-time quantitative PCR were used to identify and validate differentially expressed genes.

Main Results:

• Exercise improved premature aging phenotypes (skin, tremor) and enhanced hippocampal vascularization and BDNF gene expression in SAMP8 mice.
• 34 genes were identified as differentially expressed in aging mice and modulated by exercise, primarily involved in extracellular matrix maintenance.
• Validation confirmed changes in collagen type 1 alpha 1 (col1a1), col1a2, fibromodulin (fmod), prostaglandin D(2) synthase (ptgds), and aldehyde dehydrogenase (Aldh1a2) expression.

Conclusions:

• Adult voluntary wheel running can ameliorate aging-related physical and molecular changes in the hippocampus.
• Exercise may prevent or delay age-related gene expression alterations and processes in the brain, particularly those involving the extracellular matrix.
• The SAMP8 mouse model and identified genes provide valuable insights into the molecular basis of brain aging and exercise intervention.