title: Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer's Disease.
abstract: The mouse model of Alzheimer's disease (AD), Tg2576 mice (APP), has provided valuable information, such as the role of the metallothionein (MT) family in their behavioral and amyloidosis phenotypes. In this study, we further characterize the role of MT-1 by crossingMt1-overexpressing mice with Tg2576 mice (APPTgMT). In 14-month-old mice, MT-1(/2) protein levels were dramatically increased byMt1overexpression throughout the cortex (Cx), which showed a prominent caudal-rostral gradient, and the hippocampus (HC). There was a trend for MT-1(/2) immunostaining to be increased in the areas surrounding the amyloid plaques in control male mice but not inMt1-overexpressing mice. Gliosis was elicited by the amyloid plaques, but the effects ofMt1overexpression were modest. However, in hippocampal western blots the microglial marker Iba-1 was increased in old male APPTgMT mice compared to APP-wild type (APPWT) mice, and the opposite was observed in young mice. Hippocampal CA1 neuronal loss was observed in Tg2576 mice, but was unaffected byMt1overexpression. Aging increased Zn and Cu levels differently depending on brain area, sex, and genotype. Thus, the effects ofMt1overexpression on the phenotype of Tg2576 mice here studied are modest.
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. gemma.comes@uab.cat.
authors.forename: Gemma
authors.initials: G
authors.lastname: Comes
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. ymanso.sanz@gmail.com.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Manso
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Anna.Escrig@uab.cat.
authors.forename: Anna
authors.initials: A
authors.lastname: Escrig
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Olaya.Fernandez@uab.cat.
authors.forename: Olaya
authors.initials: O
authors.lastname: Fernandez-Gayol
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Paula.Sanchis@uab.cat.
authors.forename: Paula
authors.initials: P
authors.lastname: Sanchis
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. amalia.molinero@uab.cat.
authors.forename: Amalia
authors.initials: A
authors.lastname: Molinero
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. merce.giralt@uab.cat.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Giralt
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. javier.Carrasco@uab.cat.
authors.forename: Javier
authors.initials: J
authors.lastname: Carrasco
authors.affiliation: Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Juan.Hidalgo@uab.cat.
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D003300:Copper / Q000378:metabolism; D004195:Disease Models, Animal; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology; D008668:Metallothionein / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D015032:Zinc / Q000378:metabolism
chemical_list: D008670:Metals; D003300:Copper; D008668:Metallothionein; D015032:Zinc
keywords: Alzheimer’s disease; CA1 neuronal loss; Tg2576; amyloid plaques; gliosis; metallothionein-1; metals