Long-Term Exercise Modulates Hippocampal Gene Expression in Senescent Female Mice
Long-Term Exercise Modulates Hippocampal Gene Expression in Senescent Female Mice
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DOI：
10.3233/jad-121264
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Kaliman, Perla
中科院分区：
文献类型：
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作者：
Jesus Alvarez-Lopez, Maria;Castro-Freire, Marco;Kaliman, Perla
衰老加速的 SAMP8 小鼠被认为是一种有用的非转基因模型，可用于研究进行性认知衰退和阿尔茨海默病 (AD)。使用 SAMR1 小鼠作为对照，我们探讨了 10 个月大的雌性 SAMP8 小鼠 6 个月自愿轮跑的效果。与对照组相比，SAMP8 小鼠的运动改善了与过早衰老相关的表型特征（即肤色和身体震颤），并增强了海马体的血管化和 BDNF 基因表达。为了确定与长期运动对大脑衰老有反应相关的基因，我们对久坐的 SAMP8 (P8sed)、SAMR1 (R1sed) 和运动的 SAMP8 (P8run) 小鼠的海马体进行了全基因组微阵列研究。 P8sed 与 R1sed 中差异表达的基因被认为是推定的衰老标记 (i)，P8run 与 P8sed 中差异表达的基因被认为是运动调节的基因 (ii)。在两个比较（i和ii）中差异表达的基因被认为是对体育锻炼有反应的推定衰老基因。我们鉴定了 34 个符合这两个标准的基因。基因本体分析表明它们主要参与细胞外基质维持相关的功能。选定的基因通过实时定量 PCR 测定进行验证，即。例如，1 型胶原蛋白 α 1 (col1a1)、1 型胶原蛋白 α 2 (col1a2)、纤维调节蛋白 (fmod)、前列腺素 D(2) 合酶 (ptgds) 和乙醛脱氢酶 (Aldh1a2)。总的来说，我们的研究表明，成年期的运动训练可以预防或延迟高危受试者的基因表达改变和与海马衰老相关的过程。
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.