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

Ariane Sharif, Véronique Duhem-Tonnelle, Cécile Allet, Marc Baroncini, Anne Loyens, Julie Kerr-Conte, Francis Collier, Serge Blond, Sergio R. Ojeda, Marie Pierre Junier, Vincent Prevot

    Research output: Contribution to journalArticle

    40 Scopus citations

    Abstract

    Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuronglia 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.

    Original languageEnglish (US)
    Pages (from-to)362-379
    Number of pages18
    JournalGLIA
    Volume57
    Issue number4
    DOIs
    StatePublished - 2009

    Keywords

    • Cerebral cortex
    • Glial cells
    • Growth factor
    • Hypothalamus
    • Neuron-glial interactions

    ASJC Scopus subject areas

    • Neurology
    • Cellular and Molecular Neuroscience

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    Sharif, A., Duhem-Tonnelle, V., Allet, C., Baroncini, M., Loyens, A., Kerr-Conte, J., Collier, F., Blond, S., Ojeda, S. R., Junier, M. P., & Prevot, V. (2009). Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain. GLIA, 57(4), 362-379. https://doi.org/10.1002/glia.20762