Perinatal DHA Supplementation Alters Brain Functional Organization in a Piglet Model

FASEB JOURNAL(2020)

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摘要
Docosahexaenoic acid (DHA) is the most abundant n3 poly‐unsaturated fatty acid (PUFA) in the central nervous system that accumulates most rapidly during the third trimester of gestation and early postnatal life. While maternal fish intake and infant DHA status were suggested positively associated with cognitive function during early years from observational studies, intervention trials supplementing DHA during gestation and/or lactation yielded controversial findings in healthy infants. This study aims to investigate whether maternal supplementation of DHA during late gestation and lactation imparts advantages to fiber bundle maturation and functional organization of the developing brain which may contribute to cognitive development in healthy offspring using a piglet model. Pig is a robust translational animal model for brain research that shares similar growth patterns with human infants. Pregnant sows (n=8) were fed a control diet only (CON) or diet containing DHA (DHA, 75 mg/kg BW/day) from late gestation until lactation. DHA supplementation drastically increased colostrum n3‐PUFA levels including DHA. Healthy piglets (n=7 in CON and DHA) underwent magnetic resonance imaging (MRI) in a 3.0 Tesla General Electric scanner to acquire anatomical, diffusion tensor imaging (DTI), and resting‐state functional MRI (rs‐fMRI) data at weaning (21d old). Maternal DHA supplementation during gestation and lactation increased fiber tract length (p=.0061) and tend to increase fractional anisotropy value (p=.0906) in the hippocampus of the offspring compared to the piglets born to CON sows. The mean diffusivity showed no difference between the two groups (p>.05). This indicated that DHA may enhance myelination of fiber bundles and improve fiber tract integrity that potentiates efficient neural communication. The subsequent rs‐fMRI analysis examined the six resting‐state networks including executive control network, cerebellum network, visual network, sensorimotor network, auditory network, and default mode network. Using sparse dictionary learning approach, we found that piglets from DHA‐fed sows had a significant 11.9 % enhanced connectivity within visual network encompassing primary, secondary, and associative visual cortex (p=.0012). In addition, piglets born to DHA‐fed sows showed a 10.1% decrease in functional connectivity in the sensorimotor network encompassing primary motor cortex, somatosensory association cortex, and premotor cortex compared to that of CON piglets (p=.0001). This suggested that DHA may result in higher intrinsic activity in the visual system and prevent activation of sensorimotor network in the absence of external stimuli. In conclusion, maternal DHA supplementation during late gestation and lactation may enhance fiber tract integrity and alter brain functional organization of the offspring which resulted in increased exploratory behaviors and improved learning and memory function we observed previously. Support or Funding Information The study was supported by Georgia Experimental Agricultural Station, HATCH #GEO00795, faculty research grant from Office or Research at the UGA, and Division of Research at PCOM‐19131. DHA was kindly provided by DSM, Inc
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brain,piglet model
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