Journal of Alzheimer's Disease
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Home > Overexpression of Metallothionein-1 Modulates the Phenotype of the Tg2576 Mouse Model of Alzheimer's Disease.

TitleOverexpression of Metallothionein-1 Modulates the Phenotype of the Tg2576 Mouse Model of Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2016
AuthorsManso, Y, Comes, G, López-Ramos, JC, Belfiore, M, Molinero, A, Giralt, M, Carrasco, J, Adlard, PA, Bush, AI, Delgado-García, JMaría, Hidalgo, J
JournalJ Alzheimers Dis
Volume51
Issue1
Pagination81-95
Date Published2016
ISSN1875-8908
KeywordsAge Factors, Alzheimer Disease, Amyloid beta-Protein Precursor, Animals, Anxiety, Disease Models, Animal, Exploratory Behavior, Female, Gene Expression Regulation, Humans, Male, Matrix Metalloproteinase 16, Maze Learning, Metallothionein, Mice, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Mutation, Phenotype, Psychomotor Disorders
Abstract

Alzheimer's disease (AD) is the most commonly diagnosed dementia, where signs of neuroinflammation and oxidative stress are prominent. In this study we intend to further characterize the roles of the antioxidant, anti-inflammatory, and heavy metal binding protein, metallothionein-1 (MT-1), by crossing Mt1 overexpressing mice with a well-known mouse model of AD, Tg2576 mice, which express the human amyloid-β protein precursor (hAβPP) with the Swedish K670N/M671L mutations. Mt1 overexpression increased overall perinatal survival, but did not affect significantly hAβPP-induced mortality and weight loss in adult mice. Amyloid plaque burden in ∼14-month-old mice was increased by Mt1 overexpression in the hippocampus but not the cortex. Despite full length hAβPP levels and amyloid plaques being increased by Mt1 overexpression in the hippocampus of both sexes, oligomeric and monomeric forms of Aβ, which may contribute more to toxicity, were decreased in the hippocampus of females and increased in males. Several behavioral traits such as exploration, anxiety, and learning were altered in Tg2576 mice to various degrees depending on the age and the sex. Mt1 overexpression ameliorated the effects of hAβPP on exploration in young females, and potentiated those on anxiety in old males, and seemed to improve the rate of spatial learning (Morris water maze) and the learning elicited by a classical conditioning procedure (eye-blink test). These results clearly suggest that MT-1 may be involved in AD pathogenesis.

DOI10.3233/JAD-151025
Alternate JournalJ. Alzheimers Dis.
PubMed ID26836194
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Source URL: https://www.j-alz.com/content/overexpression-metallothionein-1-modulates-phenotype-tg2576-mouse-model-alzheimers-disease