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Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease
Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer’s disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperho...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690745/ https://www.ncbi.nlm.nih.gov/pubmed/33114054 http://dx.doi.org/10.3390/nu12113248 |
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author | Nieraad, Hendrik de Bruin, Natasja Arne, Olga Hofmann, Martine C. J. Schmidt, Mike Saito, Takashi Saido, Takaomi C. Gurke, Robert Schmidt, Dominik Till, Uwe Parnham, Michael J. Geisslinger, Gerd |
author_facet | Nieraad, Hendrik de Bruin, Natasja Arne, Olga Hofmann, Martine C. J. Schmidt, Mike Saito, Takashi Saido, Takaomi C. Gurke, Robert Schmidt, Dominik Till, Uwe Parnham, Michael J. Geisslinger, Gerd |
author_sort | Nieraad, Hendrik |
collection | PubMed |
description | Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer’s disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel App(NL-G-F) knock-in mouse model for AD, simulating an early stage of the disease. Methods: Urine and serum samples were analyzed using a validated LC-MS/MS method and the impact of different experimental diets on cognitive performance was studied in a comprehensive behavioral test battery. Finally, we analyzed brain samples immunohistochemically in order to assess amyloid-β (Aβ) plaque deposition. Results: Behavioral testing data indicated subtle cognitive deficits in App(NL-G-F) compared to C57BL/6J wild type mice. Elevation of homocysteine and homocysteic acid, as well as counteracting dietary interventions, mostly did not result in significant effects on learning and memory performance, nor in a modified Aβ plaque deposition in 35-week-old App(NL-G-F) mice. Conclusion: Despite prominent Aβ plaque deposition, the App(NL-G-F) model merely displays a very mild AD-like phenotype at the investigated age. Older App(NL-G-F) mice should be tested in order to further investigate potential effects of hyperhomocysteinemia and dietary interventions. |
format | Online Article Text |
id | pubmed-7690745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76907452020-11-27 Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease Nieraad, Hendrik de Bruin, Natasja Arne, Olga Hofmann, Martine C. J. Schmidt, Mike Saito, Takashi Saido, Takaomi C. Gurke, Robert Schmidt, Dominik Till, Uwe Parnham, Michael J. Geisslinger, Gerd Nutrients Article Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer’s disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel App(NL-G-F) knock-in mouse model for AD, simulating an early stage of the disease. Methods: Urine and serum samples were analyzed using a validated LC-MS/MS method and the impact of different experimental diets on cognitive performance was studied in a comprehensive behavioral test battery. Finally, we analyzed brain samples immunohistochemically in order to assess amyloid-β (Aβ) plaque deposition. Results: Behavioral testing data indicated subtle cognitive deficits in App(NL-G-F) compared to C57BL/6J wild type mice. Elevation of homocysteine and homocysteic acid, as well as counteracting dietary interventions, mostly did not result in significant effects on learning and memory performance, nor in a modified Aβ plaque deposition in 35-week-old App(NL-G-F) mice. Conclusion: Despite prominent Aβ plaque deposition, the App(NL-G-F) model merely displays a very mild AD-like phenotype at the investigated age. Older App(NL-G-F) mice should be tested in order to further investigate potential effects of hyperhomocysteinemia and dietary interventions. MDPI 2020-10-23 /pmc/articles/PMC7690745/ /pubmed/33114054 http://dx.doi.org/10.3390/nu12113248 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nieraad, Hendrik de Bruin, Natasja Arne, Olga Hofmann, Martine C. J. Schmidt, Mike Saito, Takashi Saido, Takaomi C. Gurke, Robert Schmidt, Dominik Till, Uwe Parnham, Michael J. Geisslinger, Gerd Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease |
title | Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease |
title_full | Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease |
title_fullStr | Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease |
title_full_unstemmed | Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease |
title_short | Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease |
title_sort | impact of hyperhomocysteinemia and different dietary interventions on cognitive performance in a knock-in mouse model for alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690745/ https://www.ncbi.nlm.nih.gov/pubmed/33114054 http://dx.doi.org/10.3390/nu12113248 |
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