Early detection of redox imbalance in the APPswe/PS1dE9 mouse model of Alzheimer’s disease by in vivo electron paramagnetic resonance imaging
| Autor: | Miho C. Emoto, Hirotada Fujii, Shun Shimohama, Hideo Sato-Akaba, Katsuya Kawanishi, Naoya Hamaue, Hisashi Koshino |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Antioxidant medicine.medical_treatment Mice Transgenic Oxidative phosphorylation medicine.disease_cause Biochemistry Superoxide dismutase Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease In vivo Physiology (medical) Internal medicine medicine Animals chemistry.chemical_classification Reactive oxygen species Amyloid beta-Peptides biology Electron Spin Resonance Spectroscopy Brain Neurodegenerative Diseases Glutathione Disease Models Animal 030104 developmental biology Endocrinology chemistry biology.protein Cell activation Oxidation-Reduction 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Free Radical Biology and Medicine. 172:9-18 |
| ISSN: | 0891-5849 |
| Popis: | Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. Deposition of amyloid-β (Aβ) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by the generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and is known to occur early in its course. Several reports have suggested a relationship between changes in redox status and AD pathology, including progressive Aβ deposition, glial cell activation, and inflammation. In the present study, we employed a newly designed three-dimensional continuous-wave digital electron paramagnetic resonance (EPR) imager with a blood-brain barrier (BBB)-permeable redox-sensitive piperidine nitroxide probe, 4-oxo-2,2,6,6-tetramethyl-piperidine-d16-1-oxyl, for early detection of changed brain redox status. Using this system, we noninvasively compared age-matched 7-month-old AD model mice with normal littermates (WT mice). The obtained brain redox images of AD and WT mice clearly showed impaired brain redox status of AD mice compared to WT, suggesting that oxidative damage had already increased in 7-month-old AD mice compared with age-matched WT mice. The pathological changes in 7-month-old mice in this study were detected earlier than in previous studies in which only AD mice older than 9 months of age could be imaged. Since EPR images suggested that oxidative damage was already increased in 7-month-old AD mice compared to age-matched WT mice, we also evaluated antioxidant levels and the activity of superoxide dismutase (SOD) in brain tissue homogenates of 7-month-old AD and WT mice. Compared to WT mice, decreased levels of glutathione and mitochondrial SOD activity were found in AD mice, which supports the EPR imaging results indicating impaired brain redox status. These results indicate that the EPR imaging method developed in this study is useful for early noninvasive detection of altered brain redox status due to oxidative disease. |
| Databáze: | OpenAIRE |
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