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Study of the GABA receptors affecting neuronal degeneration in the subjects with Alzheimer's disease

GABA 受体影响阿尔茨海默病患者神经元变性的研究

基本信息

批准号：
21591502
负责人：
MIZUKAMI Katsuyoshi
金额：
$ 2.83万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

The results of our studies are presented here. Ubiquilin 1 is shuttle protein, which modulates the expression of the GABA receptors. We examined immunohistochemically ubiquilin in the hippocampi from the controls and Alzheimer's disease (AD). In early AD cases, the intensity of ubiquilin staining appeared more robust in the pyramidal cells in CA3 and CA2 and dentate granular cells. In the majority of severely affected cases, a remarkable decrease in ubiquilin staining was observed throughout the hippocampus. These results suggest that up-regulating ubiquilin marks a compensatory response to early neurodegenerative changes. Next, We examined beta amyloid (Ab) pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible AD but with no detectable [C-11]PiB PET retention ([C-11]PiB (-)) when imaged 17 months prior to death. The [C-11]PiB (-) case indicates that certain levels of Ab concentration are required to produce a positive [C-11]PiB PET signal. In the third study, we immunohistochemically examined the 5-HT1A receptor protein, which can contribute to impaired cognitive function in AD and may reduce in early AD by PET study, in the hippocampus. Our data demonstrate that hippocampal 5-HT1A receptors are mainly preserved until advanced stage of AD. It is unlikely 5-HT1A is associated with neuronal degeneration in AD brain.

我们的研究结果在此介绍。泛素 1 是穿梭蛋白，可调节 GABA 受体的表达。我们通过免疫组织化学方法检查了对照组和阿尔茨海默病 (AD) 的海马中的泛素。在早期 AD 病例中，CA3 和 CA2 的锥体细胞以及齿状颗粒细胞的泛素染色强度显得更强。在大多数严重受影响的病例中，观察到整个海马体中泛素染色显着减少。这些结果表明，上调泛素标志着对早期神经退行性变化的补偿反应。接下来，我们检查了一名个体的 β 淀粉样蛋白 (Ab) 病理学，该个体临床诊断为可能患有路易体痴呆和可能患有 AD，但在死亡前 17 个月进行成像时未检测到 [C-11]PiB PET 滞留 ([C-11]PiB (-))。 [C-11]PiB (-) 情况表明需要一定水平的 Ab 浓度才能产生阳性 [C-11]PiB PET 信号。在第三项研究中，我们通过免疫组织化学方法检测了海马体中的 5-HT1A 受体蛋白，该蛋白可能导致 AD 中认知功能受损，并且通过 PET 研究可能会减少早期 AD 中的认知功能。我们的数据表明，海马 5-HT1A 受体主要保留到 AD 晚期。 5-HT1A 不太可能与 AD 大脑中的神经元变性有关。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study.

DOI：
10.1007/s00401-012-0943-2
发表时间：
2012-03
期刊：
Acta neuropathologica
影响因子：
12.7
作者：
Ikonomovic MD;Abrahamson EE;Price JC;Hamilton RL;Mathis CA;Paljug WR;Debnath ML;Cohen AD;Mizukami K;DeKosky ST;Lopez OL;Klunk WE
通讯作者：
Klunk WE

An immunohistochemical study of the serotonin 1A receptor in the hippocampus of subjects with Alzheimer's disease.