Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer’s Disease
Open accessAbstract
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.
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In Tg2576 mice, a significant decrease in the thickness of the CA1 pyramidal cell layer has been demonstrated by Nissl staining, but no report directly links intraneuronal Aβ accumulation and neurodegeneration.
“While no report directly links intraneuronal Aβ accumulation and neurodegeneration in these mice, a significant decrease in the thickness of the CA1 pyramidal cell layer has been demonstrated by Nissl staining [93].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [93]
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Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models
Wirths, O., & Zampar, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218144 · Cited by 75 · see citing works
“While no report directly links intraneuronal Aβ accumulation and neurodegeneration in these mice, a significant decrease in the thickness of the CA1 pyramidal cell layer has been demonstrated by Nissl staining [93].”
Background
- Authors
- Comes, G., Manso, Y., Escrig, A., Fernandez-Gayol, O., Sanchis, P., Molinero, A., Giralt, M., Carrasco, J., & Hidalgo, J.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
- Corresponding author
- Hidalgo, Juan
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2017-01-26
- Volume
- 18
- Issue
- 2
- Pages
- 251
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5343787
- OpenAlex
- W2581186916
- Cited by
- 10
- References
- 38
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 1
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Economía y Competitividad Ministerio de Economía y Competitividad (SAF2011-23272, SAF2014-56546-R)
- Fundació La Marató de TV3 (20142210)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- metallothionein-1, transgenic mice, Alzheimer's disease, gliosis, amyloid plaques, hippocampus, microglia, zinc, copper, aging, sex differences, APP overexpression
- MeSH terms
- Alzheimer Disease, Animals, Brain, Copper, Disease Models, Animal, Gliosis, Metallothionein, Metals, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Zinc, Microglia, Mice, CA1 Region, Hippocampal, Plaque, Amyloid
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