Impaired migration signaling in the hippocampus following prenatal hypoxia

M. Hava Golan, Revital Mane, Gabriela Molczadzki, Michal Zuckerman, Vered Kaplan-Louson, Mahmoud Huleihel, J. Regino Perez-Polo

    Research output: Contribution to journalArticle

    27 Scopus citations

    Abstract

    Prenatal hypoxia ischemia is a major cause of neurodevelopmental impairment in the newborn, associated with risk for motor, behavioral and cognitive impaired outcomes. We used an established mouse model of maternal hypoxia to examine the immediate molecular responses of signaling pathways associated with both cell death and neurogenesis. We also characterized responses to maternal pre-treatment with MgSO4. Maternal hypoxia at embryonic day 17 (E17) failed to trigger inflammation or cell death in fetal brain at 24 h after hypoxia. However, maternal hypoxia decreased levels of neuronal migration signaling: Reelin (53% of control), Disabled 1 (Dab1, 77% of control), and amyloid precursor protein (APP, 64% of control) 2 h after the insult. These changes persisted for 24 h. At later times, Reelin levels in hippocampi of newborns in the maternal hypoxia-treated group increased compared to controls. Full protection from maternal hypoxia effects on hippocampal Reelin levels resulted from maternal pre-treatment with MgSO4. Hypoxia and MgSO4 increased radial and lateral migration distance in the CA1 four days after the insult, while in the DG the hypoxia treatment alone increased migration. Maternal hypoxia and MgSO4 pre-treatment also stimulated hippocampal expression of genes related to neurogenesis, such as BDNF and NeuroD4. Taken together, the long-term neurodevelopmental outcome of prenatal and perinatal hypoxia may depend on perturbation of developmental signals that affect neuronal migration.

    Original languageEnglish (US)
    Pages (from-to)511-522
    Number of pages12
    JournalNeuropharmacology
    Volume57
    Issue number5-6
    DOIs
    StatePublished - Oct 2009

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    Keywords

    • 14-3-3ε
    • APP
    • Dab1
    • Magnesium-sulfate
    • Reelin

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Pharmacology

    Cite this

    Golan, M. H., Mane, R., Molczadzki, G., Zuckerman, M., Kaplan-Louson, V., Huleihel, M., & Perez-Polo, J. R. (2009). Impaired migration signaling in the hippocampus following prenatal hypoxia. Neuropharmacology, 57(5-6), 511-522. https://doi.org/10.1016/j.neuropharm.2009.07.028