Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites. (27th November 2015)

• Record Type: Journal Article
• Authors: Sakayori, Nobuyuki; Kikkawa, Takako; Tokuda, Hisanori; Kiryu, Emiko; Yoshizaki, Kaichi; Kawashima, Hiroshi; Yamada, Tetsuya; Arai, Hiroyuki; Kang, Jing X.; Katagiri, Hideki; Shibata, Hiroshi; Innis, Sheila M.; Arita, Makoto; Osumi, Noriko
• Is Part Of: Stem cells. Volume 34:Number 2(2016:Feb.)
• Page Start: 470
• Page End: 482
• Publication Date: 2015-11-27
• Subjects: Neural stem cells -- Arachidonic acid -- Docosahexaenoic acid -- Epoxides -- Anxiety -- Metabolomics; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2246
• Languages: English
• ISSNs: 1066-5099

Abstract

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. Abstract : Omega-6 and omega-3 polyunsaturated fatty acids are essential nutrients. Although several studies have suggested that a balanced dietary omega-6:omega-3 ratio is essential for normal brain development, the underlying cellular and molecular mechanism is poorly understood. Here we shows that maternal consumption of an omega-6 rich/omega-3 poor diet impairs offspring's neocortical neuronal layer formation, and reveals its cellular and molecular mechanism; epoxy metabolites of omega-6 and omega-3 regulate the fate of neural stem cells (NSCs). We also show that these offspring demonstrate increased anxiety-related behavior. Our results raise important concerns regarding the increased consumption of such a modern diet, particularly during pregnancy.