title: Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.
abstract: Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy.
authors.affiliation: School of Medicine, Department of Medical Physiology, University CEU San Pablo, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain.|Fundación De Investigación HM Hospitales, Plaza Del Conde Del Valle De Súchil 16, Madrid, Spain.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Puche
authors.affiliation: School of Medicine, Department of Medical Physiology, University CEU San Pablo, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain.|Fundación De Investigación HM Hospitales, Plaza Del Conde Del Valle De Súchil 16, Madrid, Spain.
authors.forename: Úrsula
authors.initials: Ú
authors.lastname: Muñoz
authors.affiliation: Fundación De Investigación HM Hospitales, Plaza Del Conde Del Valle De Súchil 16, Madrid, Spain.|Tecnologico De Monterrey (TEC), Escuela De Medicina, Monterrey, Mexico.
authors.forename: Mariano
authors.initials: M
authors.lastname: García-Magariño
authors.affiliation: School of Medicine, Department of Medical Physiology, University CEU San Pablo, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Sádaba
authors.affiliation: Fundación De Investigación HM Hospitales, Plaza Del Conde Del Valle De Súchil 16, Madrid, Spain.|Tecnologico De Monterrey (TEC), Escuela De Medicina, Monterrey, Mexico.
authors.forename: Inma
authors.initials: I
authors.lastname: Castilla-Cortázar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004487:Edema / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use*; D007858:Learning / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000066829:Neuroprotection / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000975:Antioxidants; D006360:Heat-Shock Proteins; D007334:Insulin-Like Growth Factor I
keywords: IGF-1; apoptosis; autophagy; gene expression; heat shock proteins; learning and memory; magnetic resonance imaging; neurodegeneration; neuroprotection; oxidative damage