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ID 57809
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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 Kakenhi
Higaki, Yusuke Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kakenhi
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 Kakenhi
Abstract
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.
Keywords
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
Published Date
2018-07-25
Publication Title
Molecular Imaging and Biology
Volume
volume21
Issue
issue3
Publisher
Springer
Start Page
519
End Page
528
ISSN
1536-1632
NCID
AA1170000X
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
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author
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DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1007/s11307-018-1253-4
License
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
Funder Name
Japan Society for the Promotion of Science
助成番号
26670562
16K15583