Format

Send to

Choose Destination
Int J Mol Sci. 2017 Jan 26;18(2). pii: E251. doi: 10.3390/ijms18020251.

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

Author information

1
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. gemma.comes@uab.cat.
2
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. ymanso.sanz@gmail.com.
3
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Anna.Escrig@uab.cat.
4
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Olaya.Fernandez@uab.cat.
5
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Paula.Sanchis@uab.cat.
6
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. amalia.molinero@uab.cat.
7
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. merce.giralt@uab.cat.
8
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. javier.Carrasco@uab.cat.
9
Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Juan.Hidalgo@uab.cat.

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 crossing Mt1-overexpressing mice with Tg2576 mice (APPTgMT). In 14-month-old mice, MT-1(/2) protein levels were dramatically increased by Mt1 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 Mt1-overexpressing mice. Gliosis was elicited by the amyloid plaques, but the effects of Mt1 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 Mt1 overexpression. Aging increased Zn and Cu levels differently depending on brain area, sex, and genotype. Thus, the effects of Mt1 overexpression on the phenotype of Tg2576 mice here studied are modest.

KEYWORDS:

Alzheimer’s disease; CA1 neuronal loss; Tg2576; amyloid plaques; gliosis; metallothionein-1; metals

PMID:
28134760
PMCID:
PMC5343787
DOI:
10.3390/ijms18020251
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center