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Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease
Amyloid precursor protein (APP) transgenic animal models of Alzheimer’s disease have become versatile tools for basic and translational research. However, there is great heterogeneity of histological, biochemical, and functional data between transgenic mouse lines, which might be due to different tr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395433/ https://www.ncbi.nlm.nih.gov/pubmed/30853883 http://dx.doi.org/10.3389/fnins.2019.00137 |
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author | Höfling, Corinna Shehabi, Emira Kuhn, Peer-Hendrik Lichtenthaler, Stefan F. Hartlage-Rübsamen, Maike Roßner, Steffen |
author_facet | Höfling, Corinna Shehabi, Emira Kuhn, Peer-Hendrik Lichtenthaler, Stefan F. Hartlage-Rübsamen, Maike Roßner, Steffen |
author_sort | Höfling, Corinna |
collection | PubMed |
description | Amyloid precursor protein (APP) transgenic animal models of Alzheimer’s disease have become versatile tools for basic and translational research. However, there is great heterogeneity of histological, biochemical, and functional data between transgenic mouse lines, which might be due to different transgene expression patterns. Here, the expression of human APP (hAPP) by GABAergic hippocampal interneurons immunoreactive for the calcium binding proteins parvalbumin, calbindin, calretinin, and for the peptide hormone somatostatin was analyzed in Tg2576 mice by double immunofluorescent microscopy. Overall, there was no GABAergic interneuron subpopulation that did not express the transgene. On the other hand, in no case all neurons of such a subpopulation expressed hAPP. In dentate gyrus molecular layer and in stratum lacunosum moleculare less than 10% of hAPP-positive interneurons co-express any of these interneuron markers, whereas in stratum oriens hAPP-expressing neurons frequently co-express these interneuron markers to different proportions. We conclude that these neurons differentially contribute to deficits in young Tg2576 mice before the onset of Abeta plaque pathology. The detailed analysis of distinct brain region and neuron type-specific APP transgene expression patterns is indispensable to understand particular pathological features and mouse line-specific differences in neuronal and systemic functions. |
format | Online Article Text |
id | pubmed-6395433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63954332019-03-08 Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease Höfling, Corinna Shehabi, Emira Kuhn, Peer-Hendrik Lichtenthaler, Stefan F. Hartlage-Rübsamen, Maike Roßner, Steffen Front Neurosci Neuroscience Amyloid precursor protein (APP) transgenic animal models of Alzheimer’s disease have become versatile tools for basic and translational research. However, there is great heterogeneity of histological, biochemical, and functional data between transgenic mouse lines, which might be due to different transgene expression patterns. Here, the expression of human APP (hAPP) by GABAergic hippocampal interneurons immunoreactive for the calcium binding proteins parvalbumin, calbindin, calretinin, and for the peptide hormone somatostatin was analyzed in Tg2576 mice by double immunofluorescent microscopy. Overall, there was no GABAergic interneuron subpopulation that did not express the transgene. On the other hand, in no case all neurons of such a subpopulation expressed hAPP. In dentate gyrus molecular layer and in stratum lacunosum moleculare less than 10% of hAPP-positive interneurons co-express any of these interneuron markers, whereas in stratum oriens hAPP-expressing neurons frequently co-express these interneuron markers to different proportions. We conclude that these neurons differentially contribute to deficits in young Tg2576 mice before the onset of Abeta plaque pathology. The detailed analysis of distinct brain region and neuron type-specific APP transgene expression patterns is indispensable to understand particular pathological features and mouse line-specific differences in neuronal and systemic functions. Frontiers Media S.A. 2019-02-22 /pmc/articles/PMC6395433/ /pubmed/30853883 http://dx.doi.org/10.3389/fnins.2019.00137 Text en Copyright © 2019 Höfling, Shehabi, Kuhn, Lichtenthaler, Hartlage-Rübsamen and Roßner. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Höfling, Corinna Shehabi, Emira Kuhn, Peer-Hendrik Lichtenthaler, Stefan F. Hartlage-Rübsamen, Maike Roßner, Steffen Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease |
title | Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease |
title_full | Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease |
title_fullStr | Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease |
title_full_unstemmed | Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease |
title_short | Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease |
title_sort | cell type-specific human app transgene expression by hippocampal interneurons in the tg2576 mouse model of alzheimer’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395433/ https://www.ncbi.nlm.nih.gov/pubmed/30853883 http://dx.doi.org/10.3389/fnins.2019.00137 |
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