title: Magnetic resonance imaging biomarkers of exercise-induced improvement of oxidative stress and inflammation in the brain of old high-fat-fed ApoE-/-mice.
abstract: Vascular brain lesions and atherosclerosis are two similar conditions that are characterized by increased inflammation and oxidative stress. Non-invasive imaging in a murine model of atherosclerosis showed vascular brain damage and peripheral inflammation. In this study, exercise training reduced magnetic resonance imaging-detected abnormalities, insulin resistance and markers of oxidative stress and inflammation in old ApoE-/-mice. Our results demonstrate the protective effect of exercise on neurovascular damage in the ageing brain of ApoE-/-mice.
  
  
  
  Vascular brain lesions, present in advanced atherosclerosis, share pathological hallmarks with peripheral vascular lesions, such as increased inflammation and oxidative stress. Physical activity reduces these peripheral risk factors, but its cerebrovascular effect is less documented, especially by non-invasive imaging. Through a combination of in vivo and post-mortem techniques, we aimed to characterize vascular brain damage in old ApoE-/-mice fed a high-cholesterol (HC) diet with dietary controlled intake. We then sought to determine the beneficial effects of exercise training on oxidative stress and inflammation in the brain as a treatment option in an ageing atherosclerosis mouse model. Using in vivo magnetic resonance imaging (MRI) and biological markers of oxidative stress and inflammation, we evaluated the occurrence of vascular abnormalities in the brain of HC-diet fed ApoE-/-mice >70 weeks old, its association with local and systemic oxidative stress and inflammation, and whether both can be modulated by exercise. Exercise training significantly reduced both MRI-detected abnormalities (present in 71% of untrained vs. 14% of trained mice) and oxidative stress (lipid peroxidation, 9.1 ± 1.4 vs. 5.2 ± 0.9 μmol mg-1; P < 0.01) and inflammation (interleukin-1β, 226.8 ± 27.1 vs. 182.5 ± 21.5 pg mg-1; P < 0.05) in the brain, and the mortality rate. Exercise also decreased peripheral insulin resistance, oxidative stress and inflammation, but significant associations were seen only within brain markers. Highly localized vascular brain damage is a frequent finding in this ageing atherosclerosis model, and exercise is able to reduce this outcome and improve lifespan. In vivo MRI evaluated both the neurovascular damage and the protective effect of exercise.
authors.affiliation: Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Hospital Lyon Sud, University of Lyon, University Lyon 1, Oullins, France.|Laboratoire Inter-Universitaire de Biologie de la Motricité, University of Lyon, University Lyon 1, (LIBM, EA7424), Villeurbanne, France.|Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
authors.forename: Erica N
authors.initials: EN
authors.lastname: Chirico
authors.affiliation: Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Hospital Lyon Sud, University of Lyon, University Lyon 1, Oullins, France.
authors.forename: Vanessa
authors.identifier: 0000-0001-8862-1431
authors.initials: V
authors.lastname: Di Cataldo
authors.affiliation: Lyon Neuroscience Research Centre, Université de Lyon, Université Lyon 1, CNRS UMR5292; Inserm U1028, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Chauveau
authors.affiliation: Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Hospital Lyon Sud, University of Lyon, University Lyon 1, Oullins, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Geloën
authors.affiliation: Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Hospital Lyon Sud, University of Lyon, University Lyon 1, Oullins, France.
authors.forename: David
authors.initials: D
authors.lastname: Patsouris
authors.affiliation: Laboratoire Réparation et Vieillissement, Institut de Radiobiologie Cellulaire et Moléculaire, CEA, Fontenay-aux-Roses, France.
authors.forename: Benoît
authors.identifier: 0000-0002-0146-0354
authors.initials: B
authors.lastname: Thézé
authors.affiliation: Laboratoire Inter-Universitaire de Biologie de la Motricité, University of Lyon, University Lyon 1, (LIBM, EA7424), Villeurbanne, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Martin
authors.affiliation: Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Hospital Lyon Sud, University of Lyon, University Lyon 1, Oullins, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.affiliation: Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Hospital Lyon Sud, University of Lyon, University Lyon 1, Oullins, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
authors.affiliation: Laboratoire Inter-Universitaire de Biologie de la Motricité, University of Lyon, University Lyon 1, (LIBM, EA7424), Villeurbanne, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pialoux
authors.affiliation: Cardiovascular, Metabolism, Diabetes and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Hospital Lyon Sud, University of Lyon, University Lyon 1, Oullins, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Canet-Soulas
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D053583:Interleukin-1beta; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002784:Cholesterol; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase