Region- and Age-Specific Changes in Glutamate Transport in the AβPP23 Mouse Model for Alzheimer's Disease
Abstract
Using 8- and 18-month-old AβPP23 mice, we investigated the involvement of high-affinity glutamate transporters (GLAST, GLT-1, EAAC1), vesicular glutamate transporters (VGLUT1-3) and xCT, the specific subunit of system x(c)⁻, in Alzheimer's disease (AD) pathogenesis. Transporter expression was studied in cortical and hippocampal tissue and linked to extracellular glutamate and glutamate reuptake activity as measured using in vivo microdialysis. In 8-month-old animals, we could not observe plaque formation or gliosis. Yet, in hippocampus as well as cortex GLAST and GLT-1 expression was decreased. Whereas in cortex this was accompanied by upregulated VGLUT1 expression, extracellular glutamate concentrations were decreased. Surprisingly, inhibiting glutamate reuptake with TBOA revealed increased glutamate reuptake activity in cortex of AβPP23 mice, despite decreased GLAST and GLT-1 expression, and resulted in status epilepticus in all AβPP23 mice, contrary to wildtype littermates. In hippocampus of 8-month-old AβPP23 mice, we observed increased EAAC1 expression besides the decrease in GLAST and GLT-1. Yet, glutamate reuptake activity was drastically decreased according to the decreased GLAST and GLT-1 expression. In 18-month-old AβPP23 mice, plaque formation and gliosis in cortex and hippocampus were accompanied by decreased GLT-1 expression. We also showed, for the first time, increased cortical expression of VGLUT3 and xCT together with a strong tendency towards increased corti…
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Increase of amoeboid‐like microglia occurred in both SAD and FAD.
“although increase of amoeboid‐like microglia occurred in both SAD and FAD—as previously described in AD [106, 114, 115]”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [115]
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- Authors
- Schallier, A., Smolders, I., Van Dam, D., Loyens, E., De Deyn, P. P., Michotte, A., Michotte, Y., & Massie, A.
- Affiliations
- Vrije Universiteit Brussel (BE)
- Department of Biomedical Sciences, Laboratory of Neurochemistry & Behaviour>, Institute Born-Bunge, Universiteit Antwerpen, Belgium
- Universitair Ziekenhuis Brussel (BE)
- Corresponding author
- Michotte, Yvette
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2011-04-11
- Volume
- 24
- Issue
- 2
- Pages
- 287-300
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1589269270
- Cited by
- 109
- References
- 7
- Citations by year
- 2026: 4 · 2024: 8 · 2023: 8 · 2022: 13 · 2021: 9 · 2020: 14 · 2019: 8 · 2018: 3 · 2017: 8 · 2016: 11 · 2015: 8 · 2014: 6 · 2013: 6 · 2012: 2
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- Alzheimer's disease, glutamate uptake
- MeSH terms
- Aging, Alzheimer Disease, Animals, Cerebral Cortex, Chromatography, High Pressure Liquid, Disease Models, Animal, Gene Expression Regulation, Hippocampus, Humans, Mice, Transgenic, Mutation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Glutamic Acid, Amino Acid Transport System X-AG, Excitatory Amino Acid Transporter 2, Mice
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