High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function

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Autor(es): dc.creatorOliveira, Jade de-
Autor(es): dc.creatorEngel, Daiane F.-
Autor(es): dc.creatorPaula, Gabriela C. de-
Autor(es): dc.creatorSantos, Danubia B. dos-
Autor(es): dc.creatorLopes, Jadna B.-
Autor(es): dc.creatorFarina, Marcelo-
Autor(es): dc.creatorMoreira, Eduardo L. G.-
Autor(es): dc.creatorBem, Andreza Fabro de-
Data de aceite: dc.date.accessioned2024-07-22T12:08:36Z-
Data de disponibilização: dc.date.available2024-07-22T12:08:36Z-
Data de envio: dc.date.issued2021-10-14-
Data de envio: dc.date.issued2021-10-14-
Data de envio: dc.date.issued2020-10-26-
Fonte completa do material: dc.identifierhttps://repositorio.unb.br/handle/10482/42136-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/796969-
Descrição: dc.descriptionBackground: Evidence has revealed an association between familial hypercholesterolemia and cognitive impairment. In this regard, a connection between cognitive deficits and hippocampal blood-brain barrier (BBB) breakdown was found in low-density lipoprotein receptor knockout mice (LDLr–/–), a mouse model of familial hypercholesterolemia. Objective: Herein we investigated the impact of a hypercholesterolemic diet on cognition and BBB function in C57BL/6 wild-type and LDLr–/– mice. Methods: Animals were fed with normal or high cholesterol diets for 30 days. Thus, wild-type and LDLr–/– mice were submitted to memory paradigms. Additionally, BBB integrity was evaluated in the mice’s prefrontal cortices and hippocampi. Results: A tenfold elevation in plasma cholesterol levels of LDLr–/– mice was observed after a hypercholesterolemic diet, while in wild-type mice, the hypercholesterolemic diet exposure increased plasma cholesterol levels only moderately and did not induce cognitive impairment. LDLr–/– mice presented memory impairment regardless of the diet. We observed BBB disruption as an increased permeability to sodium fluorescein in the prefrontal cortices and hippocampi and a decrease on hippocampal claudin-5 and occludin mRNA levels in both wild-type and LDLr–/– mice treated with a hypercholesterolemic diet. The LDLr–/– mice fed with a regular diet already presented BBB dysfunction. The BBB-increased leakage in the hippocampi of LDLr–/– mice was related to high microvessel content and intense astrogliosis, which did not occur in the control mice. Conclusion: Therefore, LDLr–/– mice seem to be more susceptible to cognitive impairments and BBB damage induced by exposure to a high cholesterol diet. Finally, BBB disruption appears to be a relevant event in hypercholesterolemia-induced brain alterations.-
Formato: dc.formatapplication/pdf-
Publicador: dc.publisherIOS Press-
Direitos: dc.rightsAcesso Aberto-
Direitos: dc.rights© 2020 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0).-
Palavras-chave: dc.subjectBarreira hemencefálica-
Palavras-chave: dc.subjectHipercolesterolemia familiar-
Palavras-chave: dc.subjectCamundongos-
Palavras-chave: dc.subjectMemória-
Palavras-chave: dc.subjectPrejuízo cognitivo leve-
Palavras-chave: dc.subjectNeuroinflamação-
Título: dc.titleHigh cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function-
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