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...

Full description

Bibliographic Details
Main Authors: Corinna Höfling, Emira Shehabi, Peer-Hendrik Kuhn, Stefan F. Lichtenthaler, Maike Hartlage-Rübsamen, Steffen Roßner
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-02-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnins.2019.00137/full
id doaj-61f2bb0bf6134da69a0fbca9414cdf44
record_format Article
spelling 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
collection 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
work_keys_str_mv AT corinnahofling celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT emirashehabi celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT peerhendrikkuhn celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT stefanflichtenthaler celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT stefanflichtenthaler celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT stefanflichtenthaler celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT stefanflichtenthaler celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT maikehartlagerubsamen celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
AT steffenroßner celltypespecifichumanapptransgeneexpressionbyhippocampalinterneuronsinthetg2576mousemodelofalzheimersdisease
_version_ 1725455160495308800