title: Abnormal expression of myelination genes and alterations in white matter fractional anisotropy following prenatal viral influenza infection at E16 in mice.
abstract: Prenatal viral infection has been associated with the development of schizophrenia and autism. Our laboratory has previously shown that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and late second trimester (E18) administration of influenza virus. We hypothesized that middle second trimester infection (E16) in mice may lead to a different pattern of brain gene expression and structural defects in the developing offspring. C57BL6 mice were infected on E16 with a sublethal dose of human influenza virus or sham-infected using vehicle solution. Male offspring of the infected mice were collected at P0, P14, P35, and P56, their brains removed and cerebella dissected and flash frozen. Microarray, DTI and MRI scanning, as well as qRT-PCR and SDS-PAGE and western blotting analyses were performed to detect differences in gene expression and brain atrophy. Expression of several genes associated with myelination, including Mbp, Mag, and Plp1 were found to be altered, as were protein levels of Mbp, Mag, and DM20. Brain imaging revealed significant atrophy in cerebellum at P14, reduced fractional anisotropy in white matter of the right internal capsule at P0, and increased fractional anisotropy in white matter in corpus callosum at P14 and right middle cerebellar peduncle at P56. We propose that maternal infection in mouse impacts myelination genes.
authors.affiliation: Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St. SE, Minneapolis, MN 55455, USA. fatem002@umn.edu
authors.forename: S Hossein
authors.initials: SH
authors.lastname: Fatemi
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Folsom
authors.forename: Teri J
authors.initials: TJ
authors.lastname: Reutiman
authors.forename: Desiree
authors.initials: D
authors.lastname: Abu-Odeh
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Kenichi
authors.initials: K
authors.lastname: Oishi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016880:Anisotropy; D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000821:virology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009185:Myelin Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; C047516:Plp1 protein, mouse