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ID 57809
フルテキストURL
著者
Matsuura, Yuki Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Ueda, Masashi Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University ORCID Kaken ID publons researchmap
Higaki, Yusuke Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kaken ID
Sano, Kohei Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
Saji, Hideo Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
Enomoto, Shuichi Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kaken ID
抄録
PURPOSE:
In patients with Alzheimer's disease (AD), the loss of cerebral nicotinic acetylcholine receptors (nAChRs) that are implicated in higher brain functions has been reported. However, it is unclear if nAChR deficits occur in association with cognitive impairments. The purpose of this study was to assess the relationship between nAChR deficits and cognitive impairments in a mouse model of AD (APP/PS2 mice).
PROCEDURES:
The cognitive abilities of APP/PS2 and wild-type mice (aged 2-16 months) were evaluated using the novel object recognition test. Double-tracer autoradiography analyses with 5-[125I]iodo-A-85380 ([125I]5IA: α4β2 nAChR imaging probe) and 2-deoxy-2-[18F]fluoro-D-glucose were performed in both mice of different ages. [123I]5IA-single-photon emission tomography (SPECT) imaging was also performed in both mice at 12 months of age. Furthermore, each age cohort was investigated for changes in cognitive ability and expression levels of α7 nAChRs and N-methyl-D-aspartate receptors (NMDARs).
RESULTS:
No significant difference was found between the APP/PS2 and wild-type mice at 2-6 months of age in terms of novel object recognition memory; subsequently, however, APP/PS2 mice showed a clear cognitive deficit at 12 months of age. [125I]5IA accumulation decreased in the brains of 12-month-old APP/PS2 mice, i.e., at the age at which cognitive impairments were first observed; this result was supported by a reduction in the protein levels of α4 nAChRs using Western blotting. nAChR deficits could be noninvasively detected by [123I]5IA-SPECT in vivo. In contrast, no significant changes in glycometabolism, expression levels of α7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice.
CONCLUSION:
A decrease in cerebral α4β2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology.
キーワード
Alzheimer's disease
Nicotinic acetylcholine receptors
2-Deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG)
5-[I-123]Iodo-3-[2(S)-azetidinylmethoxy]pyridine ([I-123]5IA)
APP
PS2 mice
発行日
2018-07-25
出版物タイトル
Molecular Imaging and Biology
21巻
3号
出版者
Springer
開始ページ
519
終了ページ
528
ISSN
1536-1632
NCID
AA1170000X
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
author
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1007/s11307-018-1253-4
ライセンス
https://creativecommons.org/licenses/by-nc-nd/4.0/
Citation
Matsuura, Y., Ueda, M., Higaki, Y. et al. Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer’s Disease. Mol Imaging Biol 21, 519–528 (2019) doi:10.1007/s11307-018-1253-4
助成機関名
日本学術振興会
助成番号
26670562
16K15583