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...
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doaj-61f2bb0bf6134da69a0fbca9414cdf442020-11-24T23:57:11ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-02-011310.3389/fnins.2019.00137442230Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s DiseaseCorinna Höfling0Emira Shehabi1Peer-Hendrik Kuhn2Stefan F. Lichtenthaler3Stefan F. Lichtenthaler4Stefan F. Lichtenthaler5Stefan F. Lichtenthaler6Maike Hartlage-Rübsamen7Steffen Roßner8Paul-Flechsig-Institute for Brain Research, Leipzig University, Leipzig, GermanyPaul-Flechsig-Institute for Brain Research, Leipzig University, Leipzig, GermanyInstitute of Pathology, Technical University of Munich, Munich, GermanyDeutsches Zentrum für Neurodegenerative Erkrankungen, Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyNeuroproteomics, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, GermanyInstitute for Advanced Study, Technical University of Munich, Garching, GermanyPaul-Flechsig-Institute for Brain Research, Leipzig University, Leipzig, GermanyPaul-Flechsig-Institute for Brain Research, Leipzig University, Leipzig, GermanyAmyloid 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.https://www.frontiersin.org/article/10.3389/fnins.2019.00137/fullAlzheimer’s diseaseanimal modelamyloid precursor proteinhippocampusinterneuroncalcium-binding proteins |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Corinna Höfling Emira Shehabi Peer-Hendrik Kuhn Stefan F. Lichtenthaler Stefan F. Lichtenthaler Stefan F. Lichtenthaler Stefan F. Lichtenthaler Maike Hartlage-Rübsamen Steffen Roßner |
spellingShingle |
Corinna Höfling Emira Shehabi Peer-Hendrik Kuhn Stefan F. Lichtenthaler Stefan F. Lichtenthaler Stefan F. Lichtenthaler Stefan F. Lichtenthaler Maike Hartlage-Rübsamen Steffen Roßner Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease Frontiers in Neuroscience Alzheimer’s disease animal model amyloid precursor protein hippocampus interneuron calcium-binding proteins |
author_facet |
Corinna Höfling Emira Shehabi Peer-Hendrik Kuhn Stefan F. Lichtenthaler Stefan F. Lichtenthaler Stefan F. Lichtenthaler Stefan F. Lichtenthaler Maike Hartlage-Rübsamen Steffen Roßner |
author_sort |
Corinna Höfling |
title |
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_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_sort |
cell type-specific human app transgene expression by hippocampal interneurons in the tg2576 mouse model of alzheimer’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2019-02-01 |
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. |
topic |
Alzheimer’s disease animal model amyloid precursor protein hippocampus interneuron calcium-binding proteins |
url |
https://www.frontiersin.org/article/10.3389/fnins.2019.00137/full |
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