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Effects of melatonin and age on gene expression in mouse CNS using microarray analysis.

机译:褪黑素和年龄对小鼠中枢神经系统基因表达的影响。

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The expression levels of a number of genes associated with inflammation and immune function change with advancing age. Melatonin modulates gene expression levels of several of these genes. Therefore the declining levels of melatonin associated with age may play a role in the physiological effects of aging. We used oligonucleotide microarrays to measure age-related changes in mRNA expression in the murine CNS, and to study the effect of prolonged administration of dietary melatonin upon these changes. CB6F1 male mice were fed 40 ppm melatonin for 2.1 months prior to sacrifice at age 26.5 months, and compared with both age-matched controls and young, 4.5-month-old untreated controls. Total RNA was extracted from whole brain (excluding cerebellum and brain stem) and individual samples were hybridized to Affymetrix Mouse 430-2.0 arrays. The expression of a substantial number of genes was modulated by melatonin treatment and changes in selected genes were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A subset of these genes did not change with age. Conversely, some genes modulated by age were also modulated by melatonin treatment. In general, melatonin treatment drove the expression levels of these genes closer to the expression levels detected in the younger animals. Notably, the abundance of lipocalin 2 (Lcn2) mRNA increased with age and was decreased in old animals treated with melatonin. Lcn2 is a member of the acute phase response family of proteins and its mRNA levels in the brain increase in response to inflammation. Many of the genes with expression reduced by melatonin are involved in inflammation and the immune system. This suggests that melatonin treatment may influence the inflammatory responses of old animals, driving them to resemble more closely those occurring in young animals.
机译:与炎症和免疫功能有关的许多基因的表达水平随着年龄的增长而变化。褪黑激素调节其中一些基因的基因表达水平。因此,与年龄有关的褪黑激素水平下降可能在衰老的生理效应中起作用。我们使用寡核苷酸微阵列来测量鼠类中枢神经系统中与年龄相关的mRNA表达变化,并研究长期服用饮食褪黑激素对这些变化的影响。 CB6F1雄性小鼠在26.5个月大时被处死之前,饲喂40 ppm褪黑素2.1个月,并与年龄匹配的对照组和4.5个月大的未治疗的年轻对照组进行比较。从全脑(不包括小脑和脑干)中提取总RNA,并将单个样品与Affymetrix Mouse 430-2.0阵列杂交。褪黑激素处理可调节大量基因的表达,并通过定量逆转录聚合酶链反应(qRT-PCR)验证所选基因的变化。这些基因的一个子集不会随年龄变化。相反,褪黑激素处理也调节了一些受年龄调节的基因。通常,褪黑激素治疗使这些基因的表达水平更接近年轻动物中检测到的表达水平。值得注意的是,脂蛋白2(Lcn2)mRNA的丰度随着年龄的增长而增加,而在褪黑素治疗的老年动物中则降低。 Lcn2是蛋白质急性期反应家族的成员,其脑中的mRNA水平响应炎症而增加。褪黑激素使表达降低的许多基因与炎症和免疫系统有关。这表明褪黑激素的治疗​​可能会影响老年动物的炎症反应,驱使它们更接近幼年动物的炎症反应。

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