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5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice
The accumulation of amyloid β (Aβ) in the brain is a major pathological feature of Alzheimer’s disease (AD). In our previous study, we demonstrated that coffee polyphenols (CPP) prevent cognitive dysfunction and Aβ deposition in the brain of an APP/PS2 transgenic mouse AD model. The underlying mecha...
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/PMC7071270/ https://www.ncbi.nlm.nih.gov/pubmed/32075202 http://dx.doi.org/10.3390/nu12020494 |
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author | Ishida, Keiko Misawa, Koichi Nishimura, Hitomi Hirata, Tomoya Yamamoto, Masaki Ota, Noriyasu |
author_facet | Ishida, Keiko Misawa, Koichi Nishimura, Hitomi Hirata, Tomoya Yamamoto, Masaki Ota, Noriyasu |
author_sort | Ishida, Keiko |
collection | PubMed |
description | The accumulation of amyloid β (Aβ) in the brain is a major pathological feature of Alzheimer’s disease (AD). In our previous study, we demonstrated that coffee polyphenols (CPP) prevent cognitive dysfunction and Aβ deposition in the brain of an APP/PS2 transgenic mouse AD model. The underlying mechanisms, however, remain to be elucidated. Here, we investigated the effects of the chronic administration of 5-caffeoylquinic acid (5-CQA), the most abundant component of CPP, on cognitive dysfunction in APP/PS2 mice to identify the role of CPP in Aβ elimination. Relative to the untreated controls, the mice fed a 5-CQA-supplemented diet showed significant improvements in their cognitive function assessed by Y-maze and novel object recognition tests. Histochemical analysis revealed that 5-CQA substantially reduced Aβ plaque formation and neuronal loss in the hippocampi. Moreover, 5-CQA upregulated the gene encoding low-density lipoprotein receptor-related protein 1, an Aβ efflux receptor, and normalized the perivascular localization of aquaporin 4, which facilitates Aβ clearance along the paravascular pathway. These results suggest that 5-CQA reduces Aβ deposition in the brain by modulating the Aβ clearance pathways and ameliorating cognitive decline and neuronal loss in APP/PS2 mice. Thus, 5-CQA may be effective in preventing cognitive dysfunction in AD. |
format | Online Article Text |
id | pubmed-7071270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70712702020-03-19 5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice Ishida, Keiko Misawa, Koichi Nishimura, Hitomi Hirata, Tomoya Yamamoto, Masaki Ota, Noriyasu Nutrients Article The accumulation of amyloid β (Aβ) in the brain is a major pathological feature of Alzheimer’s disease (AD). In our previous study, we demonstrated that coffee polyphenols (CPP) prevent cognitive dysfunction and Aβ deposition in the brain of an APP/PS2 transgenic mouse AD model. The underlying mechanisms, however, remain to be elucidated. Here, we investigated the effects of the chronic administration of 5-caffeoylquinic acid (5-CQA), the most abundant component of CPP, on cognitive dysfunction in APP/PS2 mice to identify the role of CPP in Aβ elimination. Relative to the untreated controls, the mice fed a 5-CQA-supplemented diet showed significant improvements in their cognitive function assessed by Y-maze and novel object recognition tests. Histochemical analysis revealed that 5-CQA substantially reduced Aβ plaque formation and neuronal loss in the hippocampi. Moreover, 5-CQA upregulated the gene encoding low-density lipoprotein receptor-related protein 1, an Aβ efflux receptor, and normalized the perivascular localization of aquaporin 4, which facilitates Aβ clearance along the paravascular pathway. These results suggest that 5-CQA reduces Aβ deposition in the brain by modulating the Aβ clearance pathways and ameliorating cognitive decline and neuronal loss in APP/PS2 mice. Thus, 5-CQA may be effective in preventing cognitive dysfunction in AD. MDPI 2020-02-14 /pmc/articles/PMC7071270/ /pubmed/32075202 http://dx.doi.org/10.3390/nu12020494 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 Ishida, Keiko Misawa, Koichi Nishimura, Hitomi Hirata, Tomoya Yamamoto, Masaki Ota, Noriyasu 5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice |
title | 5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice |
title_full | 5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice |
title_fullStr | 5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice |
title_full_unstemmed | 5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice |
title_short | 5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice |
title_sort | 5-caffeoylquinic acid ameliorates cognitive decline and reduces aβ deposition by modulating aβ clearance pathways in app/ps2 transgenic mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071270/ https://www.ncbi.nlm.nih.gov/pubmed/32075202 http://dx.doi.org/10.3390/nu12020494 |
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