Red wine consumption mitigates the cognitive impairments in low-density lipoprotein receptor knockout (LDLr^−/−) mice

ABSTRACT

Although the benefits of moderate intake of red wine in decreasing incidence of cardiovascular diseases associated to hypercholesterolemia are well recognized, there are still widespread misconceptions about its effects on the hypercholesterolemia-related cognitive impairments. Herein we investigated the putative benefits of regular red wine consumption on cognitive performance of low-density lipoprotein receptor knockout (LDLr^−/−) mice, an animal model of familial hypercholesterolemia, which display cognitive impairments since early ages. The red wine was diluted into the drinking water to a final concentration of 6% ethanol and was available for 60 days for LDLr^−/− mice fed a normal or high-cholesterol diet. The results indicated that moderate red wine consumption did not alter locomotor parameters and liver toxicity. Across multiple cognitive tasks evaluating spatial learning/reference memory and recognition/identification memory, hypercholesterolemic mice drinking red wine performed significantly better than water group, regardless of diet. Additionally, immunofluorescence assays indicated a reduction of astrocyte activation and lectin stain in the hippocampus of LDLr^−/− mice under consumption of red wine. These findings demonstrate that the moderate consumption of red wine attenuates short- and long-term memory decline associated with hypercholesterolemia in mice and suggest that it could be through a neurovascular action.

KEYWORDS:

• Hypercholesterolemia
• LDLr^−/− mice
• red wine
• cognitive impairments
• neurovascular unit
• blood-brain barrier
• memory

Acknowledgements

Some of the researchers authoring this article were supported by the Brazilian Agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Programa de Apoio aos Núcleos de Excelência (PRONEX – Project NENASC), Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC), FINEP (Financiadora de Estudos e Projetos – IBN-Net #01.06.0842-00) and INCT (Instituto Nacional de Ciência e Tecnologia) for Excitotoxicity and Neuroprotection. GCP, JO, DFE and SCL receive scholarship from CAPES or CNPq. CPF, RDP and AFB are supported by research fellowships from CNPq.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Some of the researchers authoring this article were supported by the Brazilian Agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC), Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF) and INCT (Instituto Nacional de Ciência e Tecnologia) Neuroimmunomodulation.