Les effets de l'infection prénatale H1N1 chez E16 sur les systèmes de signalisation FMRP, glutamate, GABA et Réelin dans le développement du cervelet murin

Aperçu: G.M.

L'infection virale prénatale a été identifiée comme un facteur de risque potentiel pour le développement de troubles neurodéveloppementaux tels que la schizophrénie et l'autisme.  

L'étude a caractérisé les profils de développement de marqueurs sélectionnés pour ces systèmes dans des cérébelles de souris nées de souris enceintes infectées par le virus de la grippe humaine (H1N1) .

Le cervelet a été choisi du fait des preuves émergentes selon lesquelles il joue un rôle dans l'apprentissage, la mémoire et le traitement émotionnel, tous perturbés dans l'autisme et la schizophrénie.

L'étude fournit des preuves de perturbation de la FMRP, de la glutamatérgie et de la signalisation de Reelin chez la progéniture de souris exposée qui explique les multiples anomalies cérébrales observées dans ce modèle animal.  

J Neurosci Res. 2017 May;95(5):1110-1122. doi: 10.1002/jnr.23949. Epub 2016 Oct 13.

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

Fatemi SH^1,2, Folsom TD¹, Liesch SB¹, Kneeland RE¹, Karkhane Yousefi M^1,3, Thuras PD⁴.

Author information

1

Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota.

2

Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota.

3

Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan.

4

VA Medical Center, Department of Psychiatry, Minneapolis, Minnesota.

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.

© 2016 Wiley Periodicals, Inc.

PMID: 27735078

PMCID: PMC5352480 [Available on 2017-11-01]

DOI: 10.1002/jnr.23949