The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum

S H Fatemi, Timothy D. Folsom, Stephanie B. Liesch, Rachel E. Kneeland, Mahtab Karkhane Yousefi, Paul D. Thuras

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1110-1122
Number of pages13
JournalJournal of Neuroscience Research
Volume95
Issue number5
DOIs
StatePublished - May 1 2017

Keywords

  • FMRP
  • GABA
  • Reelin
  • cerebellum
  • influenza
  • mouse

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