PUBLICATION
Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets
- Authors
- McDougall, M., Choi, J., Truong, L., Tanguay, R., Traber, M.G.
- ID
- ZDB-PUB-170625-4
- Date
- 2017
- Source
- Free radical biology & medicine 110: 250-260 (Journal)
- Registered Authors
- Tanguay, Robyn L.
- Keywords
- brain, choline, dietary supplementation, docosahexaenoic acid, mitochondria, α-tocopherol
- MeSH Terms
-
- Animals
- Antioxidants/metabolism
- Avoidance Learning
- Behavior, Animal
- Cognitive Dysfunction/metabolism*
- Cognitive Dysfunction/pathology
- Cognitive Dysfunction/physiopathology
- DNA Methylation
- Diet/methods
- Disease Models, Animal
- Docosahexaenoic Acids/deficiency*
- Embryo, Nonmammalian
- Embryonic Development/physiology
- Larva/growth & development
- Larva/metabolism*
- Lipid Peroxidation
- Locomotion
- Metabolome*
- Mitochondria/metabolism
- Mitochondria/pathology
- Oxidative Stress
- Vitamin E Deficiency/metabolism*
- Vitamin E Deficiency/pathology
- Vitamin E Deficiency/physiopathology
- Zebrafish
- PubMed
- 28645790 Full text @ Free Radic. Biol. Med.
Citation
McDougall, M., Choi, J., Truong, L., Tanguay, R., Traber, M.G. (2017) Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets. Free radical biology & medicine. 110:250-260.
Abstract
Vitamin E (α-tocopherol; VitE) is a lipophilic antioxidant required for normal embryonic development in vertebrates, but the long-term effects of embryonic VitE deficiency, and whether they are ameliorated by feeding VitE-adequate diets, remain unknown. We addressed these questions using a zebrafish (Danio rerio) model of developmental VitE deficiency followed by dietary remediation. Adult zebrafish maintained on VitE-deficient (E-) or sufficient (E+) diets were spawned to obtained E- and E+ embryos, respectively, which we evaluated up to 12 days post-fertilization (dpf). The E- group suffered significantly increased morbidity and mortality as well as altered DNA methylation status through 5 dpf when compared to E+ larvae, but upon feeding with a VitE-adequate diet from 5-12 dpf both the E- and E+ groups survived and grew normally; the DNA methylation profile also was similar between groups by 12 dpf. However, 12 dpf E- larvae still had behavioral defects. These observations coincided with sustained VitE deficiency in the E- vs. E+ larvae (p< 0.0001), despite adequate dietary supplementation. We also found in E- vs. E+ larvae continued docosahexaenoic acid (DHA) depletion (p< 0.0001) and significantly increased lipid peroxidation. Further, targeted metabolomics analyses revealed persistent dysregulation of the cellular antioxidant network, the CDP-choline pathway, and glucose metabolism. While anaerobic processes were increased, aerobic metabolism was decreased in the E- vs. E+ larvae, indicating mitochondrial damage. Taken together, these outcomes suggest embryonic VitE deficiency causes lasting behavioral impairments due to persistent lipid peroxidation and metabolic perturbations that are not resolved via later dietary VitE supplementation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping