title: The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum.
abstract: Prenatal viral infection has been identified as a potential risk factor for the development of neurodevelopmental disorders such as schizophrenia and autism. Additionally, dysfunction in gamma-aminobutyric acid, Reelin, and fragile X mental retardation protein (FMRP)-metabotropic glutamate receptor 5 signaling systems has also been demonstrated in these two disorders. In the current report, we have characterized the developmental profiles of selected markers for these systems in cerebella of mice born to pregnant mice infected with human influenza (H1N1) virus on embryonic day 16 or sham-infected controls using SDS-PAGE and Western blotting techniques and evaluated the presence of abnormalities in the above-mentioned markers during brain development. The cerebellum was selected in light of emerging evidence that it plays roles in learning, memory, and emotional processing-all of which are disrupted in autism and schizophrenia. We identified unique patterns of gene and protein expression at birth (postnatal day 0 [P0]), childhood (P14), adolescence (P35), and young adulthood (P56) in both exposed and control mouse progeny. We also identified significant differences in protein expression for FMRP, very-low-density lipoprotein receptor, and glutamic acid decarboxylase 65 and 67 kDa proteins at specific postnatal time points in cerebella of the offspring of exposed mice. Our results provide evidence of disrupted FMRP, glutamatergic, and Reelin signaling in the exposed mouse offspring that explains the multiple brain abnormalities observed in this animal model. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota.|Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: S Hossein
authors.initials: SH
authors.lastname: Fatemi
authors.affiliation: Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Folsom
authors.affiliation: Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Liesch
authors.affiliation: Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Kneeland
authors.affiliation: Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota.|Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan.
authors.forename: Mahtab
authors.initials: M
authors.lastname: Karkhane Yousefi
authors.affiliation: VA Medical Center, Department of Psychiatry, Minneapolis, Minnesota.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thuras
mesh_terms: D000367:Age Factors; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009976:Orthomyxoviridae Infections / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology* / Q000821:virology; D011973:Receptors, LDL / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D005968:Glutamate Decarboxylase; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D005680:gamma-Aminobutyric Acid; C036053:VLDL receptor; C000717127:RELN protein, human; C000717128:Reln protein, mouse
keywords: FMRP; GABA; Reelin; cerebellum; influenza; mouse