High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function
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| Glavni avtor: | |
|---|---|
| Publication Date: | 2020 |
| Drugi avtorji: | , , , , , , |
| Format: | Article |
| Jezik: | eng |
| Source: | Repositório Institucional da UnB |
| Download full: | https://repositorio.unb.br/handle/10482/42136 |
Izvleček: | 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. |
| _version_ | 1871442540877578240 |
|---|---|
| author | Oliveira, Jade de |
| author2 | Engel, Daiane F. Paula, Gabriela C. de Santos, Danubia B. dos Lopes, Jadna B. Farina, Marcelo Moreira, Eduardo L. G. Bem, Andreza Fabro de |
| author2_role | author author author author author author author |
| author_browse | Bem, Andreza Fabro de Engel, Daiane F. Farina, Marcelo Lopes, Jadna B. Moreira, Eduardo L. G. Oliveira, Jade de Paula, Gabriela C. de Santos, Danubia B. dos |
| author_facet | 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 |
| author_role | author |
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| bitstream.checksumAlgorithm.fl_str_mv | MD5 MD5 |
| bitstream.url.fl_str_mv | http://repositorio.unb.br/bitstream/10482/42136/1/ARTIGO_HighCholesterolDiet.pdf http://repositorio.unb.br/bitstream/10482/42136/2/license.txt |
| collection | Repositório Institucional da UnB |
| dc.contributor.author.fl_str_mv | 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 |
| dc.date.accessioned.fl_str_mv | 2021-10-14T12:45:36Z |
| dc.date.available.fl_str_mv | 2021-10-14T12:45:36Z |
| dc.date.issued.fl_str_mv | 2020-10-27 |
| dc.identifier.citation.fl_str_mv | 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. |
| dc.identifier.doi.pt_BR.fl_str_mv | 10.3233/JAD-200541 |
| dc.identifier.uri.fl_str_mv | https://repositorio.unb.br/handle/10482/42136 |
| dc.language.iso.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | IOS Press |
| dc.rights.driver.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.source.none.fl_str_mv | reponame:Repositório Institucional da UnB instname:Universidade de Brasília (UnB) instacron:UNB |
| dc.subject.keyword.pt_BR.fl_str_mv | Barreira hematoencefálica Hipercolesterolemia familiar Camundongos Memória Prejuízo cognitivo leve Neuroinflamação |
| dc.title.pt_BR.fl_str_mv | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function |
| dc.type.driver.fl_str_mv | info:eu-repo/semantics/article |
| dc.type.status.fl_str_mv | info:eu-repo/semantics/publishedVersion |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | UNB_d6dcc4c54aaa3c45b72e6acc7dcfcb4f |
| identifier_str_mv | 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. 10.3233/JAD-200541 |
| instacron_str | UNB |
| institution | UNB |
| instname_str | Universidade de Brasília (UnB) |
| language | eng |
| network_acronym_str | UNB |
| network_name_str | Repositório Institucional da UnB |
| oai_identifier_str | oai:repositorio.unb.br:10482/42136 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher.none.fl_str_mv | IOS Press |
| reponame_str | Repositório Institucional da UnB |
| repository.mail.fl_str_mv | repositorio@unb.br |
| repository.name.fl_str_mv | Repositório Institucional da UnB - Universidade de Brasília (UnB) |
| repository_id_str | |
| spelling | Oliveira, Jade deEngel, Daiane F.Paula, Gabriela C. deSantos, Danubia B. dosLopes, Jadna B.Farina, MarceloMoreira, Eduardo L. G.Bem, Andreza Fabro de2021-10-14T12:45:36Z2021-10-14T12:45:36Z2020-10-27OLIVEIRA, 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.https://repositorio.unb.br/handle/10482/4213610.3233/JAD-200541IOS Press© 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).info:eu-repo/semantics/openAccessHigh cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive functioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleBarreira hematoencefálicaHipercolesterolemia familiarCamundongosMemóriaPrejuízo cognitivo leveNeuroinflamaçãoBackground: 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.engreponame:Repositório Institucional da UnBinstname:Universidade de Brasília (UnB)instacron:UNBORIGINALARTIGO_HighCholesterolDiet.pdfARTIGO_HighCholesterolDiet.pdfapplication/pdf2571215http://repositorio.unb.br/bitstream/10482/42136/1/ARTIGO_HighCholesterolDiet.pdf90be1545facd932c22deb432cbf34561MD51open accessLICENSElicense.txtlicense.txttext/plain102http://repositorio.unb.br/bitstream/10482/42136/2/license.txtaed4704d04bb260d4decd80db311aaa5MD52open access10482/421362025-07-03 10:40:25.055open accessoai:repositorio.unb.br:10482/42136U3VibWlzc8OjbyBlZmV0aXZhZGEgZGUgYWNvcmRvIGNvbSBsaWNlbsOnYSBjb25jZWRpZGEgcGVsbyBhdXRvciBlL291IGRldGVudG9yIGRvcyBkaXJlaXRvcyBhdXRvcmFpcy4KRepositório InstitucionalPUBhttps://repositorio.unb.br/oai/requestrepositorio@unb.bropendoar:2025-07-03T13:40:25Repositório Institucional da UnB - Universidade de Brasília (UnB) |
| spellingShingle | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function Oliveira, Jade de Barreira hematoencefálica Hipercolesterolemia familiar Camundongos Memória Prejuízo cognitivo leve Neuroinflamação |
| status_str | publishedVersion |
| title | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function |
| title_full | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function |
| title_fullStr | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function |
| title_full_unstemmed | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function |
| title_short | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function |
| title_sort | High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function |
| topic | Barreira hematoencefálica Hipercolesterolemia familiar Camundongos Memória Prejuízo cognitivo leve Neuroinflamação |
| url | https://repositorio.unb.br/handle/10482/42136 |