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Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain

Authors

  • Ariane Sharif,

    1. Inserm, Jean-Pierre Aubert Research Centre, U837, Development and Plasticity of the Postnatal Brain, Lille Cedex, France
    2. Université de Lille 2, IMPRT, Lille, France
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    • A.S. and V.D.-T. contributed equally to this article.

  • Véronique Duhem-Tonnelle,

    1. Inserm, Jean-Pierre Aubert Research Centre, U837, Development and Plasticity of the Postnatal Brain, Lille Cedex, France
    2. Université de Lille 2, IMPRT, Lille, France
    3. Clinique de Neurochirurgie, CHRU de Lille, Hôpital Roger Salengro, Lille, France
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    • A.S. and V.D.-T. contributed equally to this article.

  • Cécile Allet,

    1. Inserm, Jean-Pierre Aubert Research Centre, U837, Development and Plasticity of the Postnatal Brain, Lille Cedex, France
    2. Université de Lille 2, IMPRT, Lille, France
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  • Marc Baroncini,

    1. Inserm, Jean-Pierre Aubert Research Centre, U837, Development and Plasticity of the Postnatal Brain, Lille Cedex, France
    2. Université de Lille 2, IMPRT, Lille, France
    3. Clinique de Neurochirurgie, CHRU de Lille, Hôpital Roger Salengro, Lille, France
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  • Anne Loyens,

    1. Inserm, Jean-Pierre Aubert Research Centre, U837, Development and Plasticity of the Postnatal Brain, Lille Cedex, France
    2. Université de Lille 2, IMPRT, Lille, France
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  • Julie Kerr-Conte,

    1. Université de Lille 2, IMPRT, Lille, France
    2. Inserm U859, Lille, France
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  • Francis Collier,

    1. Université de Lille 2, IMPRT, Lille, France
    2. Service de Gynécologie, CHRU de Lille, Hôpital Jeanne-de-Flandre, Lille, France
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  • Serge Blond,

    1. Inserm, Jean-Pierre Aubert Research Centre, U837, Development and Plasticity of the Postnatal Brain, Lille Cedex, France
    2. Université de Lille 2, IMPRT, Lille, France
    3. Clinique de Neurochirurgie, CHRU de Lille, Hôpital Roger Salengro, Lille, France
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  • Sergio R. Ojeda,

    1. Division of Neuroscience, Oregon National Primate Research Center-Oregon Health and Science University, Beaverton, Oregon
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  • Marie-Pierre Junier,

    1. Inserm U894, University of Paris 5, Hospital Sainte-Anne, Department of Anatomopathology, Paris, France
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  • Vincent Prevot

    Corresponding author
    1. Inserm, Jean-Pierre Aubert Research Centre, U837, Development and Plasticity of the Postnatal Brain, Lille Cedex, France
    2. Université de Lille 2, IMPRT, Lille, France
    • Inserm U837, Bâtiment Biserte, Place de Verdun, 59045 Lille Cedex, France
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Abstract

Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuron–glia communication. Although both astrocytes and deregulation of erbB functions have been implicated in the pathogenesis of many common human brain disorders, erbB signaling in native human brain astrocytes has never been explored. Taking advantage of our ability to perform primary cultures from the cortex and the hypothalamus of human fetuses, we conducted a thorough analysis of erbB signaling in human astrocytes. We showed that human cortical astrocytes express erbB1, erbB2, and erbB3, whereas human hypothalamic astrocytes express erbB1, erbB2, and erbB4 receptors. Ligand-dependent activation of different erbB receptor heterodimeric complexes in these two populations of astrocytes translated into different morphological and proliferative responses. Although morphological plasticity was more pronounced in hypothalamic astrocytes than in cortical astrocytes, the former showed a lower mitogenic potential. Decreasing erbB4 expression via siRNA-mediated gene knockdown revealed that erbB4 constitutively restrains basal proliferative activity in hypothalamic astrocytes. We further show that treatment of human astrocytes with a protein kinase C activator results in rapid tyrosine phosphorylation of erbB receptors that involves cleavage of endogenous membrane bound erbB ligands by metalloproteinases. Together, these results indicate that erbB signaling in primary human brain astrocytes is functional, region-specific, and can be activated in a paracrine and/or autocrine manner. In addition, by revealing that some aspects of astroglial erbB signaling are different between human and rodents, our results provide a molecular framework to explore the potential involvement of astroglial erbB signaling deregulation in human brain disorders. © 2008 Wiley-Liss, Inc.

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