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Stem Cells. 2016 Feb;34(2):470-82. doi: 10.1002/stem.2246. Epub 2015 Nov 27.

Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites.

Author information

1
Department of Developmental Neuroscience, Center for Neuroscience, United Centers for Advanced Research and Translational Medicine, Tohoku University School of Medicine, Miyagi, Japan.
2
Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan.
3
Institute for Health Care Science, Suntory Wellness Ltd, Osaka, Japan.
4
Department of Metabolism and Diabetes, Tohoku University School of Medicine, Miyagi, Japan.
5
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
6
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Massachusetts, USA.
7
Department of Paediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
8
Laboratory for Metabolomics, Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.

Abstract

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients. Although several studies have suggested that a balanced dietary n-6:n-3 ratio is essential for brain development, the underlying cellular and molecular mechanism is poorly understood. Here, we found that feeding pregnant mice an n-6 excess/n-3 deficient diet, which reflects modern human diets, impairsed neocortical neurogenesis in the offspring. This impaired neurodevelopment occurs through a precocious fate transition of neural stem cells from the neurogenic to gliogenic lineage. A comprehensive mediator lipidomics screen revealed key mediators, epoxy metabolites, which were confirmed functionally using a neurosphere assay. Importantly, although the offspring were raised on a well-balanced n-6:n-3 diet, they exhibited increased anxiety-related behavior in adulthood. These findings provide compelling evidence that excess maternal consumption of n-6 PUFAs combined with insufficient intake of n-3 PUFAs causes abnormal brain development that can have long-lasting effects on the offspring's mental state.

KEYWORDS:

Anxiety; Arachidonic acid; Docosahexaenoic acid; Epoxides; Metabolomics; Neural stem cells

PMID:
26580686
DOI:
10.1002/stem.2246
[Indexed for MEDLINE]
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