Physical activity-associated gene expression signature in nonhuman primate motor cortex.

Physical activity-associated gene expression signature in nonhuman primate motor cortex.
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DOI:
10.1038/oby.2011.328
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发表时间:
2012-03
期刊:
影响因子:
6.9
通讯作者:
Mirnics, Karoly
Mirnics, Karoly
中科院分区:
医学2区
文献类型:
--
作者:
Mitchell, Amanda C.;Leak, Rehana K.;Garbett, Krassimira;Zigmond, Michael J.;Cameron, Judy L.;Mirnics, Karoly

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已经确定,体重增加和体重减轻受到活动水平的严重影响。在这项研究中,我们假设运动皮层表现出明显的身体活动相关基因表达谱,这可能是与运动相关的体重变化的基础。使用DNA微阵列,我们分析了一组14只雌性恒河猴(Macaca mulatta)的运动皮质中的基因表达,这些恒河猴具有广泛的稳定体力活动水平。我们发现大脑中的神经生长因子信号和营养传感转录本与体力活动高度相关。对AKT3表达变化(神经元存活和营养感测顶点的基因)的随访显示,总AKT、磷酸化AKT和叉头盒O3(FOXO3)(AKT的主要下游效应物之一)的蛋白水平增加。此外,我们通过定量聚合酶链反应(qPCR)成功验证了其他三个基因(cereblon(CRBN)、起源识别复合物亚基4样和丙酮酸脱氢酶4(PDK4))。我们的结论是,这些基因在运动皮层的身体活动相关的途径是重要的,可能是身体活动相关的体重和神经保护的变化至关重要。
It has been established that weight gain and weight loss are heavily influenced by activity level. In this study, we hypothesized that the motor cortex exhibits a distinct physical activity-associated gene expression profile, which may underlie changes in weight associated with movement. Using DNA microarrays we profiled gene expression in the motor cortex of a group of 14 female rhesus monkeys (Macaca mulatta) with a wide range of stable physical activity levels. We found that neuronal growth factor signaling and nutrient sensing transcripts in the brain were highly correlated with physical activity. A follow-up of AKT3 expression changes (a gene at the apex of neuronal survival and nutrient sensing) revealed increased protein levels of total AKT, phosphorylated AKT, and forkhead box O3 (FOXO3), one of AKT’s main downstream effectors. In addition, we successfully validated three other genes via quantitative polymerase chain reaction (qPCR) (cereblon (CRBN), origin recognition complex subunit 4-like, and pyruvate dehydrogenase 4 (PDK4)). We conclude that these genes are important in the physical activity-associated pathway in the motor cortex, and may be critical for physical activity-associated changes in body weight and neuroprotection.
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