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 Fátima-
Autor(es): dc.creatorPaula, Gabriela Cristina de-
Autor(es): dc.creatorGodoi, Danúbia Bonfanti dos Santos de-
Autor(es): dc.creatorLopes, Jadna Bogado-
Autor(es): dc.creatorFarina, Marcelo-
Autor(es): dc.creatorMoreira, Eduardo Luiz Gasnhar-
Autor(es): dc.creatorBem, Andreza Fabro de-
Data de aceite: dc.date.accessioned2025-08-21T15:53:02Z-
Data de disponibilização: dc.date.available2025-08-21T15:53:02Z-
Data de envio: dc.date.issued2022-12-14-
Data de envio: dc.date.issued2022-12-14-
Data de envio: dc.date.issued2019-
Fonte completa do material: dc.identifierhttp://www.repositorio.ufop.br/jspui/handle/123456789/15918-
Fonte completa do material: dc.identifierhttps://content.iospress.com/articles/journal-of-alzheimers-disease/jad200541-
Fonte completa do material: dc.identifierhttps://doi.org/10.3233/JAD-200541-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1026494-
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-
Idioma: dc.languageen-
Direitos: dc.rightsrestrito-
Palavras-chave: dc.subjectFamilial hypercholesterolemia-
Palavras-chave: dc.subjectMemory impairment-
Palavras-chave: dc.subjectMild cognitive impairment-
Palavras-chave: dc.subjectNeuroinflammation-
Título: dc.titleHigh cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function.-
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