DHA-enriched fish oil ameliorates deficits in cognition associated with menopause and the APOE4 genotype in rodents

Pontifex, Matthew G., Martinsen, Anneloes, Saleh, Rasha N. M., Harden, Glenn, Fox, Chris, Muller, Michael, Vauzour, David and Minihane, Anne-Marie (2022) DHA-enriched fish oil ameliorates deficits in cognition associated with menopause and the APOE4 genotype in rodents. Nutrients, 14 (9). ISSN 2072-6643

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Abstract

Female APOE4 carriers have a greater predisposition to developing Alzheimer’s disease (AD) compared to their male counterparts, which may partly be attributed to menopause. We previously reported that a combination of menopause and APOE4 led to an exacerbation of cognitive and neurological deficits, which were associated with reduced brain DHA and DHA:AA ratio. Here, we explored whether DHA-enriched fish oil (FO) supplementation mitigated the detrimental impact of these risk factors. Whilst DHA-enriched fish oil improved recognition memory (NOR) in APOE4 VCD (4-vinylcyclohexene diepoxide)-treated mice (p < 0.05), no change in spatial working memory (Y-maze) was observed. FO supplementation increased brain DHA and nervonic acid and the DHA:AA ratio. The response of key bioenergetic and blood–brain barrier related genes and proteins provided mechanistic insights into these behavioural findings, with increased BDNF protein concentration as well as mitigation of aberrant Erβ, Cldn1 and Glut-5 expression in APOE4 mice receiving fish oil supplementation (p < 0.05). In conclusion, supplementation with a physiologically relevant dose of DHA-enriched fish oil appears to offer protection against the detrimental effects of menopause, particularly in “at-risk” APOE4 female carriers.

Item Type: Article
Additional Information: This research was funded by the Alzheimer’s Society, grant number AS-PhD-2015-023.
Uncontrolled Keywords: 4-vinylcyclohexanediepoxide,alzheimer’s disease,bdnf,glut-5,apolipoprotein e,arachidonic acid,brain,docosahexaenoic acid,oestrogen,oestrogen receptor,food science,nutrition and dietetics ,/dk/atira/pure/subjectarea/asjc/1100/1106
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 20 Apr 2022 15:30
Last Modified: 30 May 2022 00:21
URI: https://ueaeprints.uea.ac.uk/id/eprint/84698
DOI: 10.3390/nu14091698

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