Characterization of the role of metallothionein-3 in an animal model of Alzheimer's disease

Yasmina Manso, Javier Carrasco, Gemma Comes, Gabriele Meloni, Paul A. Adlard, Ashley I. Bush, Milan Vašák, Juan Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)

Abstract

Among the dementias, Alzheimer's disease (AD) is the most commonly diagnosed, but there are still no effective drugs available for its treatment. It has been suggested that metallothionein-3 (MT-3) could be somehow involved in the etiology of AD, and in fact very promising results have been found in in vitro studies, but the role of MT-3 in vivo needs further analysis. In this study, we analyzed the role of MT-3 in a mouse model of AD, Tg2576 mice, which overexpress human Amyloid Precursor Protein (hAPP) with the Swedish mutation. MT-3 deficiency partially rescued the APP-induced mortality of females, and mildly affected APP-induced changes in behavior assessed in the hole-board and plus-maze tests in a gender-dependent manner. Amyloid plaque burden and/or hAPP expression were decreased in the cortex and hippocampus of MT-3-deficient females. Interestingly, exogenously administered Zn7MT-3 increased soluble Ab40 and Ab42 and amyloid plaques and gliosis, particularly in the cortex, and changed several behavioral traits (increased deambulation and exploration and decreased anxiety). These results highlight that the control of the endogenous production and/or action of MT-3 could represent a powerful therapeutic target in AD. © 2012 Springer Basel AG.
Original languageEnglish
Pages (from-to)3683-3700
JournalCellular and Molecular Life Sciences
Volume69
DOIs
Publication statusPublished - 1 Nov 2012

Keywords

  • Alzheimer's disease
  • Amyloid plaques
  • Behavior
  • Body weight
  • Gliosis
  • Metallothionein
  • Metals
  • Survival
  • Tg2576

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