Dietary alpha linolenic acid in pregnant mice and during weaning increases brain docosahexaenoic acid and improves recognition memory in the offspring

Alicia Leikin-Frenkel, Sigal Liraz-Zaltsman, Kenneth S. Hollander, Dana Atrakchi, Orly Ravid, Daniel Rand, Michal Kandel-Kfir, Hila Israelov, Hofit Cohen, Yehuda Kamari, Aviv Shaish, Dror Harats, Michal Schnaider-Beeri, Itzik Cooper

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Docosahexaenoic acid (DHA) is critical for normal brain development and function. DHA is in danger of being significantly reduced in the human food supply, and the question of whether its metabolic precursor, the essential n-3 alpha linolenic acid (ALA) during pregnancy, can support fetal brain DHA levels for optimal neurodevelopment, is fundamental. Female mice were fed either ALA-enriched or Control diet during pregnancy and lactation. The direct effect of maternal dietary ALA on lipids was analyzed in liver, red blood cells, brain and brain vasculature, together with genes of fatty acid metabolism and transport in three-week-old offspring. The long-term effect of maternal dietary ALA on brain fatty acids and memory was studied in 19-week-old offspring. Three-week-old ALA offspring showed higher levels of n-3 fatty acids in liver, red blood cell, blood-brain barrier (BBB) vasculature and brain parenchyma, DHA enrichment in brain phospholipids and higher gene and protein expression of the DHA transporter, major facilitator superfamily domain containing 2a, compared to Controls. 19-week-old ALA offspring showed higher brain DHA levels and better memory performance than Controls. The increased brain DHA levels induced by maternal dietary ALA during pregnancy-lactation, together with the up-regulated levels of major facilitator superfamily domain containing 2a, may indicate a mode for greater DHA uptake with long-term impact on better memory in ALA offspring.

Original languageEnglish
Article number108597
JournalJournal of Nutritional Biochemistry
Volume91
DOIs
StatePublished - May 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021

Funding

IC and ALF are supported by a grant for innovation from the Sheba Medical Center . IC is supported by Ministry of Science and Technology grant no. 3-13576 and Defense Threat Reduction Agency- Joint Science & Technology Office for Chemical & Biological Defense grant no. 11816372 and by the Nehemia Rubin Excellence in Biomedical Research – The TELEM Program supported by the Aaron Gutwirth Fund . IC and ALF designed the study, analyzed the results and wrote the manuscript. ALF performed all the lipid analysis, AS collaborated in the animal tissues excision, KSH performed the NOR tests. SLZ analyzed the NOR data. DA, MKK, OR, DR and HI performed the experiments. HC, YK, AS, DH and MSB contributed to the writing of the manuscript. All authors reviewed and approved the final version of the manuscript. We thank Sonia Khan from the Mount Sinai School of Medicine, NY, for her important support in the blood vessels isolation procedure. Authors declare no conflict of interests. IC and ALF are supported by a grant for innovation from the Sheba Medical Center. IC is supported by Ministry of Science and Technology grant no. 3-13576 and Defense Threat Reduction Agency- Joint Science & Technology Office for Chemical & Biological Defense grant no. 11816372 and by the Nehemia Rubin Excellence in Biomedical Research ? The TELEM Program supported by the Aaron Gutwirth Fund. The data that support the findings of this study are available from the corresponding author upon reasonable request.

FundersFunder number
Aaron Gutwirth Fund
Joint Science & Technology Office for Chemical & Biological Defense11816372
Nehemia Rubin Excellence in Biomedical Research
Nehemia Rubin Excellence in Biomedical Research ?
Sheba Medical Center
Defense Threat Reduction Agency
Ministry of science and technology, Israel3-13576

    Keywords

    • Alpha linolenic acid
    • Blood-brain barrier
    • DHA
    • Fatty acid
    • Maternal diet
    • Memory

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