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

Ji-Hong Liu, Qian Wang, Qiang-Long You, Ze-Lin Li, Neng-Yuan Hu, Yan Wang, Zeng-Lin Jin, Shu-Ji Li, Xiao-Wen Li, Jian-Ming Yang, Xin-Hong Zhu, Yi-Fan Dai, Jiang-Ping Xu, Xiao-Chun Bai and Tian-Ming Gao ()
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Ji-Hong Liu: Southern Medical University
Qian Wang: Southern Medical University
Qiang-Long You: Southern Medical University
Ze-Lin Li: Southern Medical University
Neng-Yuan Hu: Southern Medical University
Yan Wang: Nanjing Medical University
Zeng-Lin Jin: Beijing Institute of Pharmacology and Toxicology
Shu-Ji Li: Southern Medical University
Xiao-Wen Li: Southern Medical University
Jian-Ming Yang: Southern Medical University
Xin-Hong Zhu: Southern Medical University
Yi-Fan Dai: Nanjing Medical University
Jiang-Ping Xu: Southern Medical University
Xiao-Chun Bai: Southern Medical University
Tian-Ming Gao: Southern Medical University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19255-1

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