Expression of the Ghrelin and Neurotensin Systems is Altered in the Temporal Lobe of Alzheimer's Disease Patients
Expression of the Ghrelin and Neurotensin Systems is Altered in the Temporal Lobe of Alzheimer's Disease Patients
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DOI：
10.3233/jad-2010-100873
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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.
Ghrelin和神经降压素（NTS）是神经内分泌肽，对食物摄入和能量稳态发挥相反的作用，但在改善记忆和学习方面具有相似的作用。Ghrelin和NTS通过具有高度进化同一性的受体介导它们的作用：两个Ghrelin G蛋白偶联受体（GPCR; GHS-R1 a/1b）和三个NTS受体，两个GPCR（NTSR 1/2）和一个非GPCR（NTSR 3）。由于ghrelin和NTS系统与能量平衡调节和认知过程密切相关，因此已提出它们在阿尔茨海默病（AD）中发生改变，阿尔茨海默病是一种受代谢状态显著影响的痴呆综合征。虽然已经证明ghrelin和NTS可以减轻AD相关的认知障碍，但尚未对AD中的这些系统进行全面分析。在这里，我们使用定量的真实的时间-RT-PCR来分析在AD中最受影响的皮质区域之一，颞回中ghrelin/NTS轴的表达。结果揭示了ghrelin及其新发现的In 2-ghrelin变体，以及负责ghrelin酰化的酶，ghrelin-O-酰基转移酶和GHS-R1 a的mRNA水平显著降低，而GHS-R1 b的表达显著增加。此外，NTSR 1和NTSR 2的表达水平在AD中显著降低，而NTS的mRNA水平仅略有下降，而NTSR 3（参与神经元凋亡）的mRNA水平没有变化。两者合计，我们的研究结果提供了第一个定量证据表明，饥饿素/NTS系统显着改变AD患者的大脑，从而表明，这些系统可能有助于在这种病理学中观察到的严重认知缺陷。
Ghrelin and neurotensin (NTS) are neuroendocrine peptides that exert opposite effects on food intake and energy homeostasis, but share comparable actions in improving memory and learning. Ghrelin and NTS mediate their effects via receptors with high evolutionary identity: two ghrelin G-protein coupled receptors (GPCRs; GHS-R1a/1b) and three NTS-receptors, two GPCRs (NTSR1/2) and one non-GPCR (NTSR3). Because ghrelin and NTS systems are tightly linked to energy balance regulation and cognitive processes, they have been proposed to be altered in Alzheimer's disease (AD), a dementia syndrome markedly influenced by the metabolic status. Although it has been demonstrated that ghrelin and NTS can attenuate AD-related cognitive impairment, a comprehensive analysis of these systems in AD has not been conducted. Here, we used quantitative real time-RT-PCR to analyze expression of the ghrelin/NTS axis in one of the cortical regions most affected in AD, the temporal gyrus. Results unveiled a striking reduction of mRNA levels for ghrelin, and its newly discovered In2-ghrelin variant, as well as for the enzyme responsible for ghrelin acylation, ghrelin-O-acyltransferase and GHS-R1a, while expression of GHS-R1b was markedly increased. In addition, expression levels of NTSR1 and NTSR2 were profoundly decreased in AD, whereas mRNA levels of NTS only declined slightly, and those of NTSR3 (which is involved in neuronal apoptosis) did not vary. Taken together, our results provide the first quantitative evidence showing that ghrelin/NTS systems are markedly altered in the brain of AD patients, thereby suggesting that these systems may contribute to the severe cognitive deficit observed in this pathology.