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Molecular Imaging and Biology

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25.07.2018 | Research Article

Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer’s Disease

verfasst von: Yuki Matsuura, Masashi Ueda, Yusuke Higaki, Kohei Sano, Hideo Saji, Shuichi Enomoto

Erschienen in: Molecular Imaging and Biology | Ausgabe 3/2019

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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.

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Titel: Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer’s Disease
verfasst von: Yuki Matsuura
Masashi Ueda
Yusuke Higaki
Kohei Sano
Hideo Saji
Shuichi Enomoto
Publikationsdatum: 25.07.2018
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 3/2019
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1253-4

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Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer’s Disease

Abstract

Purpose

Procedures

Results

Conclusion

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Springer Medizin

Abstract

Purpose

Procedures

Results

Conclusion

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