start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=6 article-no= start-page=372 end-page=378 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Noninvasive evaluation of nicotinic acetylcholine receptor availability in mouse brain using single-photon emission computed tomography with [(123)I]5IA. en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION:
Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in higher brain functions. Nuclear medical imaging is one of the useful techniques for noninvasive evaluation of physiological and pathological function in living subjects. Recent progress in nuclear medical imaging modalities enables the clear visualization of the organs of small rodents. Thus, translational research using nuclear medical imaging in transgenic mice has become possible and helps to elucidate human disease pathology. However, imaging of α4β2 nAChRs in the mouse brain has not yet been performed. The purpose of this study was to assess the feasibility of single-photon emission computed tomography (SPECT) with 5-[(123)I]iodo-3-[2(S)-azetidinylmethoxy]pyridine ([(123)I]5IA) for evaluating α4β2 nAChR availability in the mouse brain.
METHODS:
A 60-min dynamic SPECT imaging session of α4β2 nAChRs in the mouse brain was performed. The regional distribution of radioactivity in the SPECT images was compared to the density of α4β2 nAChRs measured in an identical mouse. Alteration of nAChR density in the brains of Tg2576 mice was also evaluated.
RESULTS:
The mouse brain was clearly visualized by [(123)I]5IA-SPECT and probe accumulation was significantly inhibited by pretreatment with (-)-nicotine. The regional distribution of radioactivity in SPECT images showed a significant positive correlation with α4β2 nAChR density measured in an identical mouse brain. Moreover, [(123)I]5IA-SPECT was able to detect the up-regulation of α4β2 nAChRs in the brains of Tg2576 transgenic mice.
CONCLUSIONS:
[(123)I]5IA-SPECT imaging would be a promising tool for evaluating α4β2 nAChR availability in the mouse brain and may be useful in translational research focused on nAChR-related diseases. 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=WatanabeKeiko en-aut-sei=Watanabe en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HabaraShogo en-aut-sei=Habara en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaminoShinichiro en-aut-sei=Kamino en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=5-[(123)I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([(123)I]5IA) kn-keyword=5-[(123)I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([(123)I]5IA) en-keyword=Alzheimer's disease kn-keyword=Alzheimer's disease en-keyword=Mouse kn-keyword=Mouse en-keyword=Nicotinic acetylcholine receptor (nAChR) kn-keyword=Nicotinic acetylcholine receptor (nAChR) en-keyword=Single-photon emission computed tomography (SPECT) kn-keyword=Single-photon emission computed tomography (SPECT) en-keyword=Tg2576 kn-keyword=Tg2576 END 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:
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. 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 start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=12 article-no= start-page=1338 end-page=1342 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150928 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histological and Nuclear Medical Comparison of Inflammation After Hemostasis with Non-Thermal Plasma and Thermal Coagulation en-subtitle= kn-subtitle= en-abstract= kn-abstract= The objective of this study is to examine the invasiveness of hemostasis by non-thermal plasma (NTP) compared with hemostasis by thermal coagulation (TC). The inflammation recovery process after hemostasis by TC and NTP was compared by using histological methods and nuclear medical molecular imaging. The necrotic areas in the NTP group disappeared after 5 days, whereas they remained 15 days after hemostasis in the TC group. The accumulation of 2-deoxy-2-[F-18] fluoro-D-glucopyranose (F-18-FDG), which reflects the existence of inflammatory cells, was higher in the TC group than in the NTP group on day 15. Thus, this study indicates that hemostasis by NTP is less inflammatory than TC. This report is the first to evaluate inflammation that occurred after hemostasis with medical devices noninvasively. en-copyright= kn-copyright= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamagamiDaiki en-aut-sei=Yamagami en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeKeiko en-aut-sei=Watanabe en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriAsami en-aut-sei=Mori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimuraHiroyuki en-aut-sei=Kimura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=IshikawaKenji en-aut-sei=Ishikawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriMasaru en-aut-sei=Hori en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakakitaHajime en-aut-sei=Sakakita en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkeharaYuzuru en-aut-sei=Ikehara en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= affil-num=4 en-affil=Radioisotope Research Center, Kyoto University kn-affil= affil-num=5 en-affil=Radioisotope Research Center, Kyoto University kn-affil= affil-num=6 en-affil=Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Engineering, Nagoya University kn-affil= affil-num=9 en-affil=Graduate School of Engineering, Nagoya University kn-affil= affil-num=10 en-affil=National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=11 en-affil=National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=12 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= en-keyword=hemostasis kn-keyword=hemostasis en-keyword=imaging kn-keyword=imaging en-keyword=inflammation kn-keyword=inflammation en-keyword=non-thermal plasma kn-keyword=non-thermal plasma en-keyword=positron emission tomography kn-keyword=positron emission tomography END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=3 article-no= start-page=e58022 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Essential Role of the Zinc Transporter ZIP9/SLC39A9 in Regulating the Activations of Akt and Erk in B-Cell Receptor Signaling Pathway in DT40 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The essential trace element zinc is important for all living organisms. Zinc functions not only as a nutritional factor, but also as a second messenger. However, the effects of intracellular zinc on the B cell-receptor (BCR) signaling pathway remain poorly understood. Here, we present data indicating that the increase in intracellular zinc level induced by ZIP9/SLC39A9 (a ZIP Zrt-/Irt-like protein) plays an important role in the activation of Akt and Erk in response to BCR activation. In DT40 cells, the enhancement of Akt and Erk phosphorylation following BCR activation requires intracellular zinc. To clarify this event, we used chicken ZnT5/6/7-gene-triple-knockout DT40 (TKO) cells and chicken Zip9-knockout DT40 (cZip9KO) cells. The levels of Akt and ERK phosphorylation significantly decreased in cZip9KO cells. In addition, the enzymatic activity of protein tyrosine phosphatase (PTPase) increased in cZip9KO cells. These biochemical events were restored by overexpressing the human Zip9 (hZip9) gene. Moreover, we found that the increase in intracellular zinc level depends on the expression of ZIP9. This observation is in agreement with the increased levels of Akt and Erk phosphorylation and the inhibition of total PTPase activity. We concluded that ZIP9 regulates cytosolic zinc level, resulting in the enhancement of Akt and Erk phosphorylation. Our observations provide new mechanistic insights into the BCR signaling pathway underlying the regulation of intracellular zinc level by ZIP9 in response to the BCR activation. en-copyright= kn-copyright= en-aut-name=TaniguchiMasanari en-aut-sei=Taniguchi en-aut-mei=Masanari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukunakaAyako en-aut-sei=Fukunaka en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiharaMitsue en-aut-sei=Hagihara en-aut-mei=Mitsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeKeiko en-aut-sei=Watanabe en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KaminoShinichiro en-aut-sei=Kamino en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KambeTaiho en-aut-sei=Kambe en-aut-mei=Taiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HiromuraMakoto en-aut-sei=Hiromura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University affil-num=2 en-affil= kn-affil=Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science affil-num=3 en-affil= kn-affil=Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science affil-num=4 en-affil= kn-affil=Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science affil-num=5 en-affil= kn-affil=Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science affil-num=6 en-affil= kn-affil=Graduate School of Biostudies, Kyoto University affil-num=7 en-affil= kn-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University affil-num=8 en-affil= kn-affil=Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science END