title: Increased Electron Paramagnetic Resonance Signal Correlates with Mitochondrial Dysfunction and Oxidative Stress in an Alzheimer's disease Mouse Brain.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized clinically by cognitive decline and memory loss. The pathological features are amyloid-β peptide (Aβ) plaques and intracellular neurofibrillary tangles. Many studies have suggested that oxidative damage induced by reactive oxygen species (ROS) is an important mechanism for AD progression. Our recent study demonstrated that oxidative stress could further impair mitochondrial function. In the present study, we adopted a transgenic mouse model of AD (mAPP, overexpressing AβPP/Aβ in neurons) and performed redox measurements using in vivo electron paramagnetic resonance (EPR) imaging with methoxycarbamyl-proxyl (MCP) as a redox-sensitive probe for studying oxidative stress in an early stage of pathology in a transgenic AD mouse model. Through assessing oxidative stress, mitochondrial function and cognitive behaviors of mAPP mice at the age of 8-9 months, we found that oxidative stress and mitochondrial dysfunction appeared in the early onset of AD. Increased ROS levels were associated with defects of mitochondrial and cognitive dysfunction. Notably, the in vivo EPR method offers a unique way of assessing tissue oxidative stress in living animals under noninvasive conditions, and thus holds a potential for early diagnosis and monitoring the progression of AD.
authors.affiliation: Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacology, University of Kansas, Lawrence, KS, USA.
authors.forename: Du
authors.initials: D
authors.lastname: Fang
authors.affiliation: School of Life Sciences, Beijing Normal University, Beijing, China.|Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacology, University of Kansas, Lawrence, KS, USA.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacology, University of Kansas, Lawrence, KS, USA.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Cheng Du, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Nuclear Magnetic Resonance Laboratory, Molecular Structures Group, School of Pharmacy, University of Kansas, Lawrence, KS, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Douglas
authors.affiliation: Small Animal Imaging Core, Ohio State University, Columbus, OH, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Bratasz
authors.affiliation: Department of Radiology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA.
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.affiliation: Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacology, University of Kansas, Lawrence, KS, USA.
authors.forename: Shirley ShiDu
authors.initials: SS
authors.lastname: Yan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017668:Age of Onset; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D065852:Spatial Memory / Q000502:physiology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV
keywords: Aβ accumulation; cognitive function; mitochondrial dysfunction; oxidative stress