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Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease
The pathogenesis of Alzheimer’s disease (AD) is complex and involves an imbalance between production and clearance of amyloid-ß peptides (Aß), resulting in accumulation of Aß in senile plaques. Hypercholesterolemia is a major risk factor for developing AD, with cholesterol shown to accumulate in sen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275060/ https://www.ncbi.nlm.nih.gov/pubmed/37333297 http://dx.doi.org/10.21203/rs.3.rs-3014093/v1 |
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author | Fong, Vincent Kanuri, Babunageswararao Traubert, Owen Lui, Min Patel, Shailendra B. |
author_facet | Fong, Vincent Kanuri, Babunageswararao Traubert, Owen Lui, Min Patel, Shailendra B. |
author_sort | Fong, Vincent |
collection | PubMed |
description | The pathogenesis of Alzheimer’s disease (AD) is complex and involves an imbalance between production and clearance of amyloid-ß peptides (Aß), resulting in accumulation of Aß in senile plaques. Hypercholesterolemia is a major risk factor for developing AD, with cholesterol shown to accumulate in senile plaques and increase production of Aß. ABCG4 is a member of the ATP-binding cassette transporters predominantly expressed in the CNS, and has been suggested to play a role in cholesterol and Aß efflux from the brain. In this study, we bred Abcg4 knockout (KO) with the APP(Swe,Ind) (J9) mouse model of AD to test the hypothesis that loss of Abcg4 would exacerbate the AD phenotype. Unexpectedly, no differences were observed in Novel object recognition (NOR) and Novel object placement (NOP) behavioral tests, or on histologic examinations of brain tissues for senile plaque numbers. Furthermore, clearance of radiolabeled Aß from the brains did not differ between Abcg4 KO and control mice. Metabolic testing by indirect calorimetry, glucose tolerance test (GTT) and insulin tolerance test (ITT), were also mostly similar between groups with only a few mild metabolic differences noted. Overall these data suggest that the loss of ABCG4 did not exacerbate the AD phenotype. |
format | Online Article Text |
id | pubmed-10275060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-102750602023-06-17 Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease Fong, Vincent Kanuri, Babunageswararao Traubert, Owen Lui, Min Patel, Shailendra B. Res Sq Article The pathogenesis of Alzheimer’s disease (AD) is complex and involves an imbalance between production and clearance of amyloid-ß peptides (Aß), resulting in accumulation of Aß in senile plaques. Hypercholesterolemia is a major risk factor for developing AD, with cholesterol shown to accumulate in senile plaques and increase production of Aß. ABCG4 is a member of the ATP-binding cassette transporters predominantly expressed in the CNS, and has been suggested to play a role in cholesterol and Aß efflux from the brain. In this study, we bred Abcg4 knockout (KO) with the APP(Swe,Ind) (J9) mouse model of AD to test the hypothesis that loss of Abcg4 would exacerbate the AD phenotype. Unexpectedly, no differences were observed in Novel object recognition (NOR) and Novel object placement (NOP) behavioral tests, or on histologic examinations of brain tissues for senile plaque numbers. Furthermore, clearance of radiolabeled Aß from the brains did not differ between Abcg4 KO and control mice. Metabolic testing by indirect calorimetry, glucose tolerance test (GTT) and insulin tolerance test (ITT), were also mostly similar between groups with only a few mild metabolic differences noted. Overall these data suggest that the loss of ABCG4 did not exacerbate the AD phenotype. American Journal Experts 2023-06-08 /pmc/articles/PMC10275060/ /pubmed/37333297 http://dx.doi.org/10.21203/rs.3.rs-3014093/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Fong, Vincent Kanuri, Babunageswararao Traubert, Owen Lui, Min Patel, Shailendra B. Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease |
title | Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease |
title_full | Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease |
title_fullStr | Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease |
title_full_unstemmed | Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease |
title_short | Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease |
title_sort | behavioral and metabolic and effects of abcg4 ko in the appswe,ind (j9) mouse model of alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275060/ https://www.ncbi.nlm.nih.gov/pubmed/37333297 http://dx.doi.org/10.21203/rs.3.rs-3014093/v1 |
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