Journal
REDOX BIOLOGY
Volume 8, Issue -, Pages 165-174Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2016.01.004
Keywords
Brain; Development; Docosahexaenoic acid; (H2O)-O-18; Peroxidation; Vitamin E; Mass spectrometry; Phospholipids
Categories
Funding
- National Institutes of Health [S10RR027878]
- NICHD [HD062109]
- NIEHS [ES000210]
- National Science Foundation [DGE 0965820]
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We hypothesized that vitamin E (alpha-tocopherol) is required by the developing embryonic brain to prevent depletion of highly polyunsaturated fatty acids, especially docosahexaenoic acid (DHA, 22:6), the loss of which we predicted would underlie abnormal morphological and behavioral outcomes. Therefore, we fed adult 5D zebrafish (Danio rerio) defined diets without (E-) or with added alpha-tocopherol (E+, 500 mg RRR-alpha-tocopheryl acetate/kg diet) for a minimum of 80 days, and then spawned them to obtain E and E+ embryos. The E compared with E+ embryos were 82% less responsive (p < 0.01) to a light/dark stimulus at 96 h post-fertilization (hpf), demonstrating impaired locomotor behavior, even in the absence of gross morphological defects. Evaluation of phospholipid (PL) and lysophospholipid (lyso-PL) composition using untargeted lipidomics in E compared with E+ embryos at 24, 48, 72, and 120 hpf showed that four PLs and three lyso-PLs containing docosahexaenoic acid (DHA), including lysophosphatidylcholine (LPC 22:6, required for transport of DHA into the brain, p < 0.001), were at lower concentrations in E at all time-points. Additionally, (H2O)-O-18 labeling experiments revealed enhanced turnover of LPC 22:6 (p < 0.001) and three other DHA-containing PLs in the E compared with the E+ embryos, suggesting that increased membrane remodeling is a result of PL depletion. Together, these data indicate that -tocopherol deficiency in the zebrafish embryo causes the specific depletion and increased turnover of DHA-containing PL and lyso-PLs, which may compromise DHA delivery to the brain and thereby contribute to the functional impairments observed in E embryos. (C) 2016 The Authors. Published by Elsevier B.V.
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