Acute EPA-induced learning and memory impairment in mice is prevented by DHA.

Abstract:

:Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been widely used to prevent cardiovascular disease (CVD) and treat brain diseases alone or in combination with docosahexaenoic acid (DHA). However, the impact of EPA and DHA supplementation on normal cognitive function and the molecular targets of EPA and DHA are still unknown. We show that acute administration of EPA impairs learning and memory and hippocampal LTP in adult and prepubescent mice. Similar deficits are duplicated by endogenously elevating EPA in the hippocampus in the transgenic fat-1 mouse. Furthermore, the damaging effects of EPA are mediated through enhancing GABAergic transmission via the 5-HT6R. Interestingly, DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT2CR. We conclude that EPA exhibits an unexpected detrimental impact on cognitive functions, suggesting that caution must be exercised in omega-3 fatty acid supplementation and the combination of EPA and DHA at a natural ratio is critical for learning and memory and synaptic plasticity.

journal_name

Nat Commun

journal_title

Nature communications

authors

Liu JH,Wang Q,You QL,Li ZL,Hu NY,Wang Y,Jin ZL,Li SJ,Li XW,Yang JM,Zhu XH,Dai YF,Xu JP,Bai XC,Gao TM

doi

10.1038/s41467-020-19255-1

subject

Has Abstract

pub_date

2020-10-29 00:00:00

pages

5465

issue

1

issn

2041-1723

pii

10.1038/s41467-020-19255-1

journal_volume

11

pub_type

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