High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function.
dc.contributor.author | Oliveira, Jade de | |
dc.contributor.author | Engel, Daiane Fátima | |
dc.contributor.author | Paula, Gabriela Cristina de | |
dc.contributor.author | Godoi, Danúbia Bonfanti dos Santos de | |
dc.contributor.author | Lopes, Jadna Bogado | |
dc.contributor.author | Farina, Marcelo | |
dc.contributor.author | Moreira, Eduardo Luiz Gasnhar | |
dc.contributor.author | Bem, Andreza Fabro de | |
dc.date.accessioned | 2022-12-15T21:22:00Z | |
dc.date.available | 2022-12-15T21:22:00Z | |
dc.date.issued | 2020 | pt_BR |
dc.description.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. | pt_BR |
dc.identifier.citation | OLIVEIRA, J. 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, p. 97-115, 2020. Disponível em: <https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200541>. Acesso em: 11 out. 2022. | pt_BR |
dc.identifier.doi | https://doi.org/10.3233/JAD-200541 | pt_BR |
dc.identifier.issn | 1875-8908 | |
dc.identifier.uri | http://www.repositorio.ufop.br/jspui/handle/123456789/15918 | |
dc.identifier.uri2 | https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200541 | pt_BR |
dc.language.iso | en_US | pt_BR |
dc.rights | restrito | pt_BR |
dc.subject | Familial hypercholesterolemia | pt_BR |
dc.subject | Memory impairment | pt_BR |
dc.subject | Mild cognitive impairment | pt_BR |
dc.subject | Neuroinflammation | pt_BR |
dc.title | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function. | pt_BR |
dc.type | Artigo publicado em periodico | pt_BR |
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