Expression of Somatostatin, Cortistatin, and Their Receptors, as well as Dopamine Receptors, but not of Neprilysin, are Reduced in the Temporal Lobe of Alzheimer's Disease Patients
Expression of Somatostatin, Cortistatin, and Their Receptors, as well as Dopamine Receptors, but not of Neprilysin, are Reduced in the Temporal Lobe of Alzheimer's Disease Patients
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DOI：
10.3233/jad-2010-1385
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Castano, Justo P.
中科院分区：
文献类型：
--
作者：
Gahete, Manuel D.;Rubio, Alicia;Castano, Justo P.
阿尔茨海默病（Alzheimer's disease，AD）是一种以严重认知功能障碍为特征的进行性神经退行性疾病，其主要特征是情景记忆受损。AD患者在特定脑区域中表现出淀粉样蛋白-β（A β）和过度磷酸化tau蛋白的增加的积累。此外，还发现与认知过程、A β转换和tau磷酸化明显相关的几种神经肽/神经递质轴在AD中受损，例如生长激素抑制素（SST）/皮质抑制素（CST）和多巴胺（DA）系统。然而，到目前为止，还没有精确的定量数据，这些系统在人类大脑中的AD和正常患者的表达。在这里，我们测量了定量实时PCR的SST/CST的mRNA水平，它们的受体（SST 1 -5）和DA受体（drd 1 -5），除了脑啡肽酶（SST调节酶参与A β降解）在颞叶的三个区域，最严重的受AD影响的皮质区域之一。我们的研究结果表明，SST/CST-和DA-轴的一些组件在AD患者的三个领域的分歧改变。尽管这种区域特异性调节，但在AD患者的颞叶中观察到这些系统的总体常见减少。相反，脑啡肽酶表达在AD中没有改变，这表明在AD中观察到的A β积累是由于缺乏SST对脑啡肽酶的激活，而不是其表达的减少。总的来说，我们的研究结果定义了一个全面的方案，其中减少SST，DRDS，SST配体SST和CST，可能涉及，至少部分，在AD中观察到的一些更重要的缺陷。
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive deficit, wherein the impairment of episodic memory is the major hallmark. AD patients exhibit augmented accumulation of amyloid-beta (A beta) and hyperphosphorylated tau protein in specific brain regions. In addition, several neuropeptides/neurotransmitter axes clearly associated with cognitive processes, A beta turnover, and tau phosphorylation have also been found to be impaired in AD, such as somatostatin (SST)/cortistatin (CST) and dopamine (DA) systems. However, to date there is no precise quantitative data on the expression of these systems in the human brain of AD and normal patients. Here we measured by quantitative real-time PCR the mRNA levels of SST/CST, their receptors (sst1-5) and DA receptors (drd1-5) in addition to neprilysin (a SST-regulated enzyme involved in A beta degradation) in three regions of the temporal lobe, one of the cortical regions most severely affected by AD. Our results reveal that some components of SST/CST- and DA-axes are divergently altered in the three areas of AD patients. Despite this region-specific regulation, an overall, common reduction of these systems was observed in the temporal lobe of AD patients. Conversely, neprilysin expression was not altered in AD, suggesting that A beta accumulation observed in AD is due to a lack of neprilysin activation by SST rather than to a reduction of its expression. Collectively, our results define a comprehensive scenario wherein reduction of ssts, drds, and sst ligands SST and CST, could be involved, at least in part, in some of the more important defects observed in AD.