Abstract
The abundance of docosahexaenoic acid (DHA) in the mammalian brain has generated substantial interest in the search for its roles in regulating brain functions. Our recent study with a gene/stress mouse model provided evidence to support the ability for the maternal supplement of DHA to alleviate autism-associated behavior in the offspring. DHA and arachidonic acid (ARA) are substrates of enzymatic and non-enzymatic reactions, and lipid peroxidation results in the production of 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE), respectively. In this study, we examine whether a maternal DHA-supplemented diet alters fatty acids (FAs), as well as lipid peroxidation products in the pup brain, heart and plasma by a targeted metabolite approach. Pups in the maternal DHA-supplemented diet group showed an increase in DHA and a concomitant decrease in ARA in all brain regions examined. However, significant increases in 4-HHE, and not 4-HNE, were found mainly in the cerebral cortex and hippocampus. Analysis of heart and plasma showed large increases in DHA and 4-HHE, but a significant decrease in 4-HNE levels only in plasma. Taken together, the DHA-supplemented maternal diet alters the (n-3)/(n-6) FA ratio, and increases 4-HHE levels in pup brain, heart and plasma. These effects may contribute to the beneficial effects of DHA on neurodevelopment, as well as functional changes in other body organs.
Highlights
IntroductionThe high abundance of docosahexaenoic acid (22:6n-3, DHA) in the phospholipids in brain and retina has led to an interest in the search for its functional roles in health and diseases [1]
The high abundance of docosahexaenoic acid (22:6n-3, DHA) in the phospholipids in brain and retina has led to an interest in the search for its functional roles in health and diseases [1].DHA, a fatty acid with six carbon-carbon double bonds, is important during brainMetabolites 2019, 9, 40; doi:10.3390/metabo9030040 www.mdpi.com/journal/metabolitesMetabolites 2019, 9, 40 development, as there is a “DHA accretion spurt” during the late gestational period, a time of rapid neurogenesis [2]
Pregnant mice were administered a control or a 1% DHA diet throughout gestation and lactation, and the levels of 4-HHE and 4-HNE in different regions of weaning pup brain were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the fatty acids (FAs) composition was determined by gas chromatography (GC)
Summary
The high abundance of docosahexaenoic acid (22:6n-3, DHA) in the phospholipids in brain and retina has led to an interest in the search for its functional roles in health and diseases [1]. Dietary DHA administered to mice exposed to a viral mimetic, polyriboinosinic-polyribocytidilic acid, during the gestational period, was shown to alleviate autism-associated behavior in pups [19]. Taken together, these studies are in agreement with the potential beneficial effects of dietary DHA to ameliorate neurobehavioral deficits, due to maternal stress or insults. Pregnant mice were administered a control or a 1% DHA diet throughout gestation and lactation, and the levels of 4-HHE and 4-HNE in different regions of weaning pup brain were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the FA composition was determined by gas chromatography (GC).
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