Study of the GABA receptors affecting neuronal degeneration in the subjects with Alzheimer's disease
| Project/Area Number |
21591502
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 老年精神医学 / アルツハイマー病 / 海馬 / 神経細胞変性 / GABA / 興奮毒性 / ubiquilin / βアミロイド / セロトニン / セロトニン1A受容体 / 神経変性 / 神経伝達系 |
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| Research Abstract |
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.
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Early AD pathology in a [C-11]PiB-negative case : a PiB-amyloid imaging, biochemical, and immunohistochemical study2012
Author(s)
Ikonomovic MD, Abrahamson EE, PriceJC, Hamilton RL, Mathis CA, Paljug WR, Debnath ML, Cohen AD, Mizukami K, DeKosky ST, Lopez OL, Klunk WE
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Journal Title
Acta Neuropathol
Volume: 123(3)
Pages: 433-47
Related Report
Peer Reviewed
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