High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function
| Autor: | Danúbia Bonfanti dos Santos, Gabriela Cristina de Paula, Eduardo Luiz Gasnhar Moreira, Andreza Fabro de Bem, Marcelo Farina, Jadna Bogado Lopes, Jade de Oliveira, Daiane Fátima Engel |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male memory impairment Familial hypercholesterolemia Hippocampus neuroinflammation Mice 0302 clinical medicine Cognition Camundongos Memória Gliosis Hipercolesterolemia familiar Mice Knockout familial hypercholesterolemia General Neuroscience General Medicine LDLr–/– mice Astrogliosis Psychiatry and Mental health Clinical Psychology medicine.anatomical_structure Cholesterol Blood-Brain Barrier Knockout mouse lipids (amino acids peptides and proteins) Research Article medicine.medical_specialty Hypercholesterolemia Prefrontal Cortex Blood–brain barrier High cholesterol 03 medical and health sciences mild cognitive impairment Memory Internal medicine medicine Animals Cognitive Dysfunction Neuroinflammation Memory Disorders business.industry nutritional and metabolic diseases medicine.disease Barreira hemencefálica Prejuízo cognitivo leve Diet Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Receptors LDL LDL receptor Geriatrics and Gerontology business Neuroinflamação 030217 neurology & neurosurgery Lipoprotein |
| Zdroj: | Repositório Institucional da UnB Universidade de Brasília (UnB) instacron:UNB Journal of Alzheimer's Disease |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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