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ludc web

Gabriela de Paula

Postdoctoral fellow

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High Cholesterol Diet Exacerbates Blood-Brain Barrier Disruption in LDLr-/- Mice : Impact on Cognitive Function

Author

  • Jade de Oliveira
  • Daiane F Engel
  • Gabriela C de Paula
  • Danúbia B Dos Santos
  • Jadna B Lopes
  • Marcelo Farina
  • Eduardo L G Moreira
  • Andreza F de Bem

Summary, in English

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.

Publishing year

2020

Language

English

Pages

97-115

Publication/Series

Journal of Alzheimer's disease : JAD

Volume

78

Issue

1

Document type

Journal article

Publisher

IOS Press

Keywords

  • Animals
  • Blood-Brain Barrier
  • Cholesterol/metabolism
  • Cognition
  • Cognitive Dysfunction/metabolism
  • Diet
  • Disease Models, Animal
  • Gliosis/metabolism
  • Hippocampus/metabolism
  • Hypercholesterolemia/metabolism
  • Male
  • Memory
  • Memory Disorders/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Prefrontal Cortex/metabolism
  • Receptors, LDL

Status

Published

ISBN/ISSN/Other

  • ISSN: 1387-2877