title: Maternal Fructose Consumption Disrupts Brain Development of Offspring in a Murine Model of Autism Spectrum Disorder.
abstract: ObjectiveThe objective of this study was to localize by neuroimaging the altered structural brain development of these offspring using an autism model of transgenic mice lacking contactin-associated protein-like 2 (Cntnap2).Materials and MethodsPregnant dams were randomly allocated to fructose solution (10% W/V) as only drinking fluid or water. Cntnap2 heterozygous (+/-) offspring from each group were euthanized at 6 months of age and their whole brains evaluated by magnetic resonance imaging. T2-weighted images were acquired to evaluate the volumes of 29 regions of interest involved in autism spectrum disorder (ASD) pathogenesis. Whole brains were washed and processed for Nissl staining. Mann-WhitneyUtest and one-way analysis of variance were used for statistical analysis (significance:p< 0.05).ResultsThe corpus callosum, anterior commissure, and caudate putamen were significantly smaller in Cntnap2 (+/-) male offspring exposed to fructose. No brain alterations were found in the female counterparts. Nissl staining of the caudate putamen revealed higher neuronal cell count in the male fructose offspring. Female group revealed an increase in caudate putamen neuronal cell count.ConclusionMetabolic dysregulation in pregnancy alters fetal brain development in genetically predisposed offspring. This is consistent with findings in human studies and supports the role of intrauterine factors in the etiology of autism.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Saad
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Wael
authors.initials: W
authors.lastname: Alshehri
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jun
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Talar B
authors.initials: TB
authors.lastname: Kechichian
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Gamble
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Nader
authors.initials: N
authors.lastname: Alhejaily
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Shabi
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Maged M
authors.initials: MM
authors.lastname: Costantine
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Irina
authors.initials: I
authors.lastname: Burd
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000196:embryology* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development; D005632:Fructose / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D011247:Pregnancy; D011897:Random Allocation; D012737:Sex Factors
chemical_list: C568163:CNTNAP2 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D005632:Fructose