The effects of aging on gene expression in the hypothalamus and cortex of mice
The effects of aging on gene expression in the hypothalamus and cortex of mice
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DOI：
10.1073/pnas.98.4.1930
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发表时间：
2001-02-13
影响因子：
11.1
通讯作者：
Hu, YH
中科院分区：
文献类型：
--
作者：
Jiang, CH;Tsien, JZ;Hu, YH
更好地了解大脑中衰老的分子效应可能有助于揭示有机体衰老的重要方面，以及导致与年龄相关的脑功能障碍的过程。在这项研究中，我们研究了基因表达的差异，在下丘脑和皮质的年轻和老年小鼠，通过使用高密度寡核苷酸阵列。参与神经元结构和信号传导的许多关键基因在老年下丘脑和皮质中差异表达，包括突触结合蛋白I、cAMP依赖性蛋白激酶C β、载脂蛋白E、蛋白磷酸酶2A和前列腺素D。这些蛋白质的失调可能导致与年龄相关的记忆缺陷和神经退行性疾病。此外，许多在调节神经肽代谢、淀粉样前体蛋白加工和神经元凋亡中起重要作用的蛋白酶在老年脑中上调，并且可能显著促进脑老化。最后，这些基因的一个子集，其表达受到衰老的影响，相反地受到小鼠暴露于丰富环境的影响，这表明这些基因可能在学习和记忆中发挥重要作用。
A better understanding of the molecular effects of aging in the brain may help to reveal important aspects of organismal aging, as well as processes that lead to age-related brain dysfunction. In this study, we have examined differences in gene expression in the hypothalamus and cortex of young and aged mice by using high-density oligonucleotide arrays. A number of key genes involved in neuronal structure and signaling are differentially expressed in both the aged hypothalamus and cortex, including synaptotagmin I, cAMP-dependent protein kinase C beta, apolipoprotein E, protein phosphatase 2A, and prostaglandin D. Misregulation of these proteins may contribute to age-related memory deficits and neurodegenerative diseases. In addition, many proteases that play essential roles in regulating neuropeptide metabolism, amyloid precursor protein processing, and neuronal apoptosis are up-regulated in the aged brain and likely contribute significantly to brain aging. Finally, a subset of these genes whose expression is affected by aging are oppositely affected by exposure of mice to an enriched environment, suggesting that these genes may play important roles in learning and memory.