Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory
The amyloid precursor protein APP plays a crucial role in Alzheimer pathogenesis. Its physiological functions, however, are only beginning to be unraveled. APP belongs to a small gene family, including besides APP the closely related amyloid precursor-like proteins APLP1 and APLP2, that all constitu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1028836/full |
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| author | Susanne Erdinger Irmgard Amrein Michaela Back Susann Ludewig Martin Korte Martin Korte Jakob von Engelhardt David P. Wolfer David P. Wolfer Ulrike C. Müller |
| author_facet | Susanne Erdinger Irmgard Amrein Michaela Back Susann Ludewig Martin Korte Martin Korte Jakob von Engelhardt David P. Wolfer David P. Wolfer Ulrike C. Müller |
| author_sort | Susanne Erdinger |
| collection | DOAJ |
| description | The amyloid precursor protein APP plays a crucial role in Alzheimer pathogenesis. Its physiological functions, however, are only beginning to be unraveled. APP belongs to a small gene family, including besides APP the closely related amyloid precursor-like proteins APLP1 and APLP2, that all constitute synaptic adhesion proteins. While APP and APLP2 are ubiquitously expressed, APLP1 is specific for the nervous system. Previous genetic studies, including combined knockouts of several family members, pointed towards a unique role for APLP1, as only APP/APLP1 double knockouts were viable. We now examined brain and neuronal morphology in APLP1 single knockout (KO) animals, that have to date not been studied in detail. Here, we report that APLP1-KO mice show normal spine density in hippocampal CA1 pyramidal cells and subtle alterations in dendritic complexity. Extracellular field recordings revealed normal basal synaptic transmission and no alterations in synaptic plasticity (LTP). Further, behavioral studies revealed in APLP1-KO mice a small deficit in motor function and reduced diurnal locomotor activity, while learning and memory were not affected by the loss of APLP1. In summary, our study indicates that APP family members serve both distinct and overlapping functions that need to be considered for therapeutic treatments of Alzheimer’s disease. |
| first_indexed | 2024-04-13T14:43:54Z |
| format | Article |
| id | doaj.art-ffbf24cb46bb4306b854fd2685dece4f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T14:43:54Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-ffbf24cb46bb4306b854fd2685dece4f2022-12-22T02:42:50ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-10-011510.3389/fnmol.2022.10288361028836Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memorySusanne Erdinger0Irmgard Amrein1Michaela Back2Susann Ludewig3Martin Korte4Martin Korte5Jakob von Engelhardt6David P. Wolfer7David P. Wolfer8Ulrike C. Müller9Department of Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, GermanyInstitute of Anatomy, University of Zurich and Institute of Human Movement Sciences, ETH Zurich, Zurich, SwitzerlandInstitute of Pathophysiology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyZoological Institute, Division of Cellular Neurobiology, TU Braunschweig, Braunschweig, GermanyZoological Institute, Division of Cellular Neurobiology, TU Braunschweig, Braunschweig, GermanyHelmholtz Centre for Infection Research, AG NIND, Braunschweig, GermanyInstitute of Pathophysiology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyInstitute of Anatomy, University of Zurich and Institute of Human Movement Sciences, ETH Zurich, Zurich, SwitzerlandZurich Center for Integrative Human Physiology, University of Zurich, Zurich, SwitzerlandDepartment of Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, GermanyThe amyloid precursor protein APP plays a crucial role in Alzheimer pathogenesis. Its physiological functions, however, are only beginning to be unraveled. APP belongs to a small gene family, including besides APP the closely related amyloid precursor-like proteins APLP1 and APLP2, that all constitute synaptic adhesion proteins. While APP and APLP2 are ubiquitously expressed, APLP1 is specific for the nervous system. Previous genetic studies, including combined knockouts of several family members, pointed towards a unique role for APLP1, as only APP/APLP1 double knockouts were viable. We now examined brain and neuronal morphology in APLP1 single knockout (KO) animals, that have to date not been studied in detail. Here, we report that APLP1-KO mice show normal spine density in hippocampal CA1 pyramidal cells and subtle alterations in dendritic complexity. Extracellular field recordings revealed normal basal synaptic transmission and no alterations in synaptic plasticity (LTP). Further, behavioral studies revealed in APLP1-KO mice a small deficit in motor function and reduced diurnal locomotor activity, while learning and memory were not affected by the loss of APLP1. In summary, our study indicates that APP family members serve both distinct and overlapping functions that need to be considered for therapeutic treatments of Alzheimer’s disease.https://www.frontiersin.org/articles/10.3389/fnmol.2022.1028836/fullAlzheimer diseaseAPPAPLP1amyloid precursor like proteinsynaptic plasticitybehavior |
| spellingShingle | Susanne Erdinger Irmgard Amrein Michaela Back Susann Ludewig Martin Korte Martin Korte Jakob von Engelhardt David P. Wolfer David P. Wolfer Ulrike C. Müller Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory Frontiers in Molecular Neuroscience Alzheimer disease APP APLP1 amyloid precursor like protein synaptic plasticity behavior |
| title | Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory |
| title_full | Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory |
| title_fullStr | Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory |
| title_full_unstemmed | Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory |
| title_short | Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory |
| title_sort | lack of aplp1 leads to subtle alterations in neuronal morphology but does not affect learning and memory |
| topic | Alzheimer disease APP APLP1 amyloid precursor like protein synaptic plasticity behavior |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1028836/full |
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