In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy
Damaged mitochondria may be one of the earliest manifestations of Alzheimer`s disease (AD). Since oxidative phosphorylation is a primary source of neuronal energy, unlike glycolysis-dependent energy production in inflamed glia, mitochondrial respiration could provide a selective biomarker of neurona...
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sg-ntu-dr.10356-1647952023-03-05T16:55:06Z In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy Barron, Anna M. Ji, Bin Fujinaga, Masayuki Zhang, Ming-Rong Suhara, Tetsuya Sahara, Naruhiko Aoki, Ichio Tsukada, Hideo Higuchi, Makoto Lee Kong Chian School of Medicine (LKCMedicine) Science::Biological sciences::Biochemistry Functional Neuroimaging Alzheimer's Disease Damaged mitochondria may be one of the earliest manifestations of Alzheimer`s disease (AD). Since oxidative phosphorylation is a primary source of neuronal energy, unlike glycolysis-dependent energy production in inflamed glia, mitochondrial respiration could provide a selective biomarker of neuronal deterioration in AD. Here we used a recently developed positron emission tomography (PET) probe targeting mitochondrial complex I (MC-I), 18F-BCPP-EF, to non-invasively visualize mitochondrial abnormalities in the brains of tau transgenic mice (rTg4510 TauTg). Tauopathy and neuroinflammation were visualized by PET using a tau probe 11C-PBB3 and a TSPO probe, 18F-FEBMP, respectively. A marked reduction in 18F-BCPP-EF uptake was observed in hippocampal and forebrain regions of TauTg mice, colocalizing with regions of tauopathy, neuronal damage and neuroinflammation. MC-I signals were highly correlated with atrophy assayed by MRI, but negatively associated with inflammatory signals measured by TSPO-PET, indicating that neuronal metabolic signals measured by MC-I PET were robust to inflammatory interference. MC-I may be a useful imaging biomarker to detect neuronal damage and metabolic changes with minimal interference from concomitant glial hypermetabolism. Ministry of Education (MOE) Submitted/Accepted version This work was supported by grant-in aid for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS; 15653129 to TS and MH and 19189478 to MH); Research and Development Grants for Dementia (16768966 to MH); grant-in-Aid for Science Research on Innovation Area (“Brain Protein Aging” 26117001 to NS) and Science Research (C) (15K09979 to BJ) from the Ministry of Education, Culture, Sports, Science and Technology, Japan; the strategic Research Program for Brain Science from Japan Agency for Medical Research and Development, AMED (JP18dm0107094 to TS and JP18dm0107062 to NS, and 18dm0207007h0005 and 17dm0107066h to IA); Nanyang Assistant Professorship from Nanyang Technological University Singapore (to AMB); Alzheimer’s Association (AARG-18-566427 to AMB); and Singapore Ministry of Education (2018-T1-001-041 to AMB). 2023-02-16T03:55:02Z 2023-02-16T03:55:02Z 2020 Journal Article Barron, A. M., Ji, B., Fujinaga, M., Zhang, M., Suhara, T., Sahara, N., Aoki, I., Tsukada, H. & Higuchi, M. (2020). In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy. Neurobiology of Aging, 94, 140-148. https://dx.doi.org/10.1016/j.neurobiolaging.2020.05.003 0197-4580 https://hdl.handle.net/10356/164795 10.1016/j.neurobiolaging.2020.05.003 94 140 148 en 2018-T1-001-041 Neurobiology of Aging © 2021 Elsevier Inc. All rights reserved. This paper was published in Neurobiology of Aging and is made available with permission of Elsevier Inc. application/pdf |
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Science::Biological sciences::Biochemistry Functional Neuroimaging Alzheimer's Disease Barron, Anna M. Ji, Bin Fujinaga, Masayuki Zhang, Ming-Rong Suhara, Tetsuya Sahara, Naruhiko Aoki, Ichio Tsukada, Hideo Higuchi, Makoto In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy |
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Damaged mitochondria may be one of the earliest manifestations of Alzheimer`s disease (AD). Since oxidative phosphorylation is a primary source of neuronal energy, unlike glycolysis-dependent energy production in inflamed glia, mitochondrial respiration could provide a selective biomarker of neuronal deterioration in AD. Here we used a recently developed positron emission tomography (PET) probe targeting mitochondrial complex I (MC-I), 18F-BCPP-EF, to non-invasively visualize mitochondrial abnormalities in the brains of tau transgenic mice (rTg4510 TauTg). Tauopathy and neuroinflammation were visualized by PET using a tau probe 11C-PBB3 and a TSPO probe, 18F-FEBMP, respectively. A marked reduction in 18F-BCPP-EF uptake was observed in hippocampal and forebrain regions of TauTg mice, colocalizing with regions of tauopathy, neuronal damage and neuroinflammation. MC-I signals were highly correlated with atrophy assayed by MRI, but negatively associated with inflammatory signals measured by TSPO-PET, indicating that neuronal metabolic signals measured by MC-I PET were robust to inflammatory interference. MC-I may be a useful imaging biomarker to detect neuronal damage and metabolic changes with minimal interference from concomitant glial hypermetabolism. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Barron, Anna M. Ji, Bin Fujinaga, Masayuki Zhang, Ming-Rong Suhara, Tetsuya Sahara, Naruhiko Aoki, Ichio Tsukada, Hideo Higuchi, Makoto |
format |
Article |
author |
Barron, Anna M. Ji, Bin Fujinaga, Masayuki Zhang, Ming-Rong Suhara, Tetsuya Sahara, Naruhiko Aoki, Ichio Tsukada, Hideo Higuchi, Makoto |
author_sort |
Barron, Anna M. |
title |
In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy |
title_short |
In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy |
title_full |
In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy |
title_fullStr |
In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy |
title_full_unstemmed |
In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy |
title_sort |
in vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy |
publishDate |
2023 |
url |
https://hdl.handle.net/10356/164795 |
_version_ |
1759857767765508096 |