title: Long-term exercise modulates hippocampal gene expression in senescent female mice.
abstract: The senescence-accelerated SAMP8 mouse is considered a useful non-transgenic model for studying aspects of progressive cognitive decline and Alzheimer's disease (AD). Using SAMR1 mice as controls, here we explored the effects of 6 months of voluntary wheel running in 10-month-old female SAMP8 mice. Exercise in SAMP8 mice improved phenotypic features associated with premature aging (i.e., skin color and body tremor) and enhanced vascularization and BDNF gene expression in the hippocampus compared with controls. With the aim of identifying genes involved in brain aging responsive to long-term exercise, we performed whole genome microarray studies in hippocampus from sedentary SAMP8 (P8sed), SAMR1 (R1sed), and exercised SAMP8 (P8run) mice. The genes differentially expressed in P8sed versus R1sed were considered as putative aging markers (i) and those differentially expressed in P8run versus P8sed were considered as genes modulated by exercise (ii). Genes differentially expressed in both comparisons (i and ii) were considered as putative aging genes responsive to physical exercise. We identified 34 genes which met both criteria. Gene ontology analysis revealed that they are mainly involved in functions related to extracellular matrix maintenance. Selected genes were validated by real-time quantitative PCR assays, i.e., collagen type 1 alpha 1 (col1a1), collagen type 1 alpha 2 (col1a2), fibromodulin (fmod), prostaglandin D(2) synthase (ptgds), and aldehyde dehydrogenase (Aldh1a2). As a whole, our study suggests that exercise training during adulthood may prevent or delay gene expression alterations and processes associated with hippocampal aging in at-risk subjects.
authors.affiliation: Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Alvarez-López
authors.forename: Marco
authors.initials: M
authors.lastname: Castro-Freire
authors.forename: Marta
authors.initials: M
authors.lastname: Cosín-Tomás
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanchez-Roige
authors.forename: Jaume F
authors.initials: JF
authors.lastname: Lalanza
authors.forename: Jaume
authors.initials: J
authors.lastname: Del Valle
authors.forename: Marcelina
authors.initials: M
authors.lastname: Párrizas
authors.forename: Antonio
authors.initials: A
authors.lastname: Camins
authors.forename: Merce
authors.initials: M
authors.lastname: Pallás
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Escorihuela
authors.forename: Perla
authors.initials: P
authors.lastname: Kaliman
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal / Q000502:physiology* / Q000639:trends; D011897:Random Allocation; D013997:Time Factors