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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >The Rat Prefrontal-Cortex Transcriptome: Effects of Aging and Sporadic Alzheimers DiseaseLike Pathology
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The Rat Prefrontal-Cortex Transcriptome: Effects of Aging and Sporadic Alzheimers DiseaseLike Pathology

机译:大鼠前额外-Coltex转录组:衰老和散发性阿尔茨海默氏症的影响不安全

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Alzheimers disease (AD) is the most widespread late-life dementia and involves the prefrontal cortex, a vulnerable brain region implicated in memory, emotion, cognition, and decision-making behavior. To understand the molecular differences between the effects of aging and AD on the prefrontal cortex, this study characterized the age-dependent changes in gene expression in Wistar rats (control) and OXYS rats (rodents that simulate key characteristics of sporadic AD) using RNA sequencing. We found that major altered biological processes during aging in Wistar rats were associated with immune processes. Gene expression changes during development of AD-like pathology as well as at the preclinical stage were related to neuronal plasticity, catalytic activity, lipid and immune processes, and mitochondria. A comparison of genes between data sets OXYS rats and human AD revealed similarity in expression alterations of genes related primarily to mitochondrial function; immune, endocrine, and circulatory systems; signal transduction; neuronal and synaptic processes; hypoxia; and apoptosis. Expression changes in mitochondrial processes identified in OXYS rats by RNA sequencing were confirmed by ultrastructural neuronal organelle alterations and low activity of respiratory chain complexes I, IV, and V in cortical mitochondria, suggesting that mitochondrial dysfunction appears to mediate or possibly even initiate the development of AD.
机译:阿尔茨海默氏症病(AD)是最普遍的晚期痴呆症,涉及前额外的皮质,一个易受攻击的大脑区域,涉及记忆,情感,认知和决策行为。为了了解衰老和AD效果之间的分子差异,该研究表征了使用RNA测序的Wistar大鼠(对照)和oxys大鼠基因表达的年龄依赖性变化。我们发现在Wistar大鼠中老化的主要改变的生物过程与免疫过程有关。在临床前病理学的发展过程中的基因表达改变以及临床前阶段与神经元塑性,催化活性,脂质和免疫过程以及线粒体有关。数据之间基因的比较将oxys大鼠和人AD显示出在主要针对线粒体功能相关的基因的表达改变中的相似性;免疫,内分泌和循环系统;信号转导;神经元和突触过程;缺氧;和细胞凋亡。通过超微结构神经细胞器改变和呼吸链复合物I,IV和V中的呼吸链复合物I,IV和V中的呼吸链复合物I,IV和V中的低活性来证实表达改变。皮质线粒体中的呼吸链复合物I,IV和V表明似乎介导或可能甚至启动的发起线粒体功能障碍广告。

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