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.

Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex

“…We also tested the status of oligodendrocyte function in ApoD-KO brain by measuring the protein expression levels of Ptgds, a lipocalin expressed by oligodendrocytes, related to neuronal degeneration (Taniike et al, 2002) and known to increase with age (Alvarez-Lopez et al, 2013;Chen et al, 2009). No protein up-regulation with age is observed in the WT cortex, and no age-dependent differences were found to be associated with ApoD genotype (Fig.…”

Long-term wheel running changes on sensorimotor activity and skeletal muscle in male and female mice of accelerated senescence

“…In a previous study (Álvarez-López et al 2013), we demonstrated that exercise practice improved brain vascularization and alleviated phenotypic features associated with premature aging, such us prevention of deficient skin color, tremor, and lordokyphosis. The main results obtained here demonstrate that a long-term WR intervention improved balance and muscle strength performance both in R1 and P8 mice and increased motor activity in P8 female mice.…”

“…As previously described (Álvarez-López et al 2013), all mice in the WR condition were individually accommodated in cages (15 cm high×27 cm wide×27 cm deep) containing clean sawdust and a running wheel. Sedentary-control (CON) mice were equally singlehoused as the WR mice but accommodated in cages (same size) containing only clean sawdust.…”

Aldehyde dehydrogenase (ALDH) in Alzheimer’s and Parkinson’s disease

“…Recently, in a senescence-accelerated P8 (SAMP8) mouse model of aging, the effect of 6 months voluntary wheel running was explored at the gene expression levels (Alvarez-Lopez et al 2013). One of the genes differentially expressed due to exercise was ALDH1A2 (restored to control levels) in addition to the beneficial effects such as tremor signs abolishment and hippocampal revascularization (Alvarez-Lopez et al 2013).…”

“…One of the genes differentially expressed due to exercise was ALDH1A2 (restored to control levels) in addition to the beneficial effects such as tremor signs abolishment and hippocampal revascularization (Alvarez-Lopez et al 2013).…”