start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=3
article-no=
start-page=519
end-page=528
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=20180725
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer's Disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=PURPOSE:<br/>
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).<br/>
PROCEDURES:<br/>
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: ƒ¿4ƒÀ2 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 ƒ¿7 nAChRs and N-methyl-D-aspartate receptors (NMDARs).
<br/>RESULTS:<br/>
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 ƒ¿4 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 ƒ¿7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice.<br/>
CONCLUSION:<br/>
A decrease in cerebral ƒ¿4ƒÀ2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology.
en-copyright=
kn-copyright=

en-aut-name=MatsuuraYuki
en-aut-sei=Matsuura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=UedaMasashi
en-aut-sei=Ueda
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HigakiYusuke
en-aut-sei=Higaki
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SanoKohei
en-aut-sei=Sano
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SajiHideo
en-aut-sei=Saji
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=EnomotoShuichi
en-aut-sei=Enomoto
en-aut-mei=Shuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
kn-affil=

affil-num=5
en-affil=Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
kn-affil=

affil-num=6
en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Alzheimer's disease
kn-keyword=Alzheimer's disease
en-keyword=Nicotinic acetylcholine receptors
kn-keyword=Nicotinic acetylcholine receptors
en-keyword=2-Deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG)
kn-keyword=2-Deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG)
en-keyword= 5-[I-123]Iodo-3-[2(S)-azetidinylmethoxy]pyridine ([I-123]5IA)
kn-keyword= 5-[I-123]Iodo-3-[2(S)-azetidinylmethoxy]pyridine ([I-123]5IA)
en-keyword=APP
kn-keyword=APP
en-keyword=PS2 mice
kn-keyword=PS2 mice
END