Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer's Disease

• Published in: International journal of molecular sciences Vol. 18; no. 2; p. 251
• Main Authors: Comes, Gemma, Manso, Yasmina, Escrig, Anna, Fernandez-Gayol, Olaya, Sanchis, Paula, Molinero, Amalia, Giralt, Mercedes, Carrasco, Javier, Hidalgo, Juan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26-01-2017; MDPI
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; amyloid plaques; Amyloid precursor protein; Amyloidosis; Animals; Brain - metabolism; CA1 neuronal loss; CA1 Region, Hippocampal - pathology; Copper - metabolism; Disease Models, Animal; Gliosis; Gliosis - metabolism; Gliosis - pathology; Hippocampus; Information dissemination; Metallothionein; Metallothionein - metabolism; metallothionein-1; metals; Metals - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia - metabolism; Neurons - pathology; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Plaques; Rodents; Tg2576; Western blotting; Zinc - metabolism; β-Amyloid; Alzheimer’s disease; metallothionein-1; CA1 neuronal loss; metals; gliosis; Tg2576; amyloid plaques
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18020251

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 crossing
-overexpressing mice with Tg2576 mice (APPTgMT). In 14-month-old mice, MT-1(/2) protein levels were dramatically increased by
overexpression 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 in
-overexpressing mice. Gliosis was elicited by the amyloid plaques, but the effects of
overexpression 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 by
overexpression. Aging increased Zn and Cu levels differently depending on brain area, sex, and genotype. Thus, the effects of
overexpression on the phenotype of Tg2576 mice here studied are modest.