5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice
Autor: | Keiko Ishida, Koichi Misawa, Hitomi Nishimura, Tomoya Hirata, Masaki Yamamoto, Noriyasu Ota |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: | |
Zdroj: | Nutrients, Vol 12, Iss 2, p 494 (2020) |
Druh dokumentu: | article |
ISSN: | 2072-6643 12020494 |
DOI: | 10.3390/nu12020494 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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