title: High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring.
abstract: Maternal folic acid supplementation is essential to reduce the risk of neural tube defects. We hypothesize that high levels of folic acid throughout gestation may produce neural networks more susceptible to seizure in offspring. We hence administered large doses of folic acid to rats before and during gestation and found their offspring had a 42% decrease in their seizure threshold. In vitro, acute application of folic acid or its metabolite 4Hfolate to neurons induced hyper-excitability and bursting. Cultured neuronal networks which develop in the presence of a low concentration (50 nM) of 4Hfolate had reduced capacity to stabilize their network dynamics after a burst of high-frequency activity, and an increase in the frequency of mEPSCs. Networks reared in the presence of the folic acid metabolite 5M4Hfolate developed a spontaneous, distinctive bursting pattern, and both metabolites produced an increase in synaptic density.
authors.affiliation: Complexity Science Group, Department of Physics and Astronomy, Faculty of Science, University of Calgary, Calgary, AB, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Girotto
authors.forename: Lucas
authors.initials: L
authors.lastname: Scott
authors.forename: Yosef
authors.initials: Y
authors.lastname: Avchalumov
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Harris
authors.forename: Stephanie
authors.initials: S
authors.lastname: Iannattone
authors.forename: Chris
authors.initials: C
authors.lastname: Drummond-Main
authors.forename: Rose
authors.initials: R
authors.lastname: Tobias
authors.forename: Luis
authors.initials: L
authors.lastname: Bello-Espinosa
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.forename: Jörn
authors.initials: J
authors.lastname: Davidsen
authors.forename: G Campbell
authors.initials: GC
authors.lastname: Teskey
authors.forename: Michael A
authors.initials: MA
authors.lastname: Colicos
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005865:Gestational Age; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D012640:Seizures / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016708:Synaptophysin; D005492:Folic Acid