Título:	High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function
Autor(es):	Oliveira, Jade de Engel, Daiane F. Paula, Gabriela C. de Santos, Danubia B. dos Lopes, Jadna B. Farina, Marcelo Moreira, Eduardo L. G. Bem, Andreza Fabro de
Assunto:	Barreira hemencefálica Hipercolesterolemia familiar Camundongos Memória Prejuízo cognitivo leve Neuroinflamação
Data de publicação:	27-Out-2020
Editora:	IOS Press
Referência:	OLIVEIRA, Jade de et al. High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice: impact on cognitive function. Journal of Alzheimer's Disease, v. 78, n. 1, p. 97-115, 2020. DOI: 10.3233/JAD-200541. Disponível em: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200541. Acesso em: 14 out. 2021.
Abstract:	Background: 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.
Licença:	© 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).
DOI:	10.3233/JAD-200541
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