title: Impact of maternal n-3 polyunsaturated fatty acid deficiency on dendritic arbor morphology and connectivity of developing Xenopus laevis central neurons in vivo.
abstract: Docosahexaenoic acid (DHA, 22:6n-3) is an essential component of the nervous system, and maternal n-3 polyunsaturated fatty acids (PUFAs) are an important source for brain development. Here, the impact of DHA on developing central neurons was examined using an accessible in vivo model. Xenopus laevis embryos from adult female frogs fed n-3 PUFA-adequate or deficient diets were analyzed every 10 weeks for up to 60 weeks, when frogs were then switched to a fish oil-supplemented diet. Lipid analysis showed that DHA was significantly reduced both in oocytes and tadpoles 40 weeks after deprivation, and brain DHA was reduced by 57% at 60 weeks. In vivo imaging of single optic tectal neurons coexpressing tdTomato and PSD-95-GFP revealed that neurons were morphologically simpler in tadpoles from frogs fed the deficient diet compared with the adequate diet. Tectal neurons had significantly fewer dendrite branches and shorter dendritic arbor over a 48 h imaging period. Postsynaptic cluster number and density were lower in neurons deprived of n-3 PUFA. Moreover, changes in neuronal morphology correlated with a 40% decrease in the levels of BDNF mRNA and mature protein in the brain, but not in TrkB. Importantly, switching to a fish oil-supplemented diet induced a recovery in DHA content in the frog embryos within 20 weeks and diminished the deprivation effects observed on tectal neurons of Stage 45 tadpoles. Consequently, our results indicate that DHA impacts dendrite maturation and synaptic connectivity in the developing brain, and it may be involved in neurotrophic support by BDNF.
authors: Department of Neurobiology and Behavior, University of California Irvine, Irvine, California 92697.
authors: Miki
authors: M
authors: Igarashi
authors: Department of Neurobiology and Behavior, University of California Irvine, Irvine, California 92697.
authors: Rommel A
authors: RA
authors: Santos
authors: Department of Neurobiology and Behavior, University of California Irvine, Irvine, California 92697 scohenco@uci.edu.
authors: Susana
authors: S
authors: Cohen-Cory
mesh_terms: D000818:Animals; D001001:Anura; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology* / Q000254:growth & development*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology*; D000076122:Disks Large Homolog 4 Protein; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000033:anatomy & histology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D011247:Pregnancy; D013477:Superior Colliculi / Q000166:cytology; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D015525:Fatty Acids, Omega-3; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins; D004281:Docosahexaenoic Acids
keywords: DHA; Xenopus laevis; dendrite; in vivo imaging; maternal diet; tectal neuron