title: Fetal alcohol syndrome, chemo-biology and OMICS: ethanol effects on vitamin metabolism during neurodevelopment as measured by systems biology analysis.
abstract: Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment.
authors.affiliation: Centro de Biotecnologia da Universidade Federal do Rio Grande do Sul , Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil .
authors.forename: Bruno César
authors.initials: BC
authors.lastname: Feltes
authors.forename: Joice
authors.initials: J
authors.lastname: de Faria Poloni
authors.forename: Itamar José Guimarães
authors.initials: IJ
authors.lastname: Nunes
authors.forename: Diego
authors.initials: D
authors.lastname: Bonatto
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism; D011247:Pregnancy; D014815:Vitamins / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D014815:Vitamins; D000431:Ethanol