Lymphocyte regulation of neuropeptide gene expression after neuronal injury

Authors

  • Brian D. Armstrong,

    1. Mental Retardation Research Center, Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles
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  • Zhongting Hu,

    1. Mental Retardation Research Center, Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles
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  • Catalina Abad,

    1. Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
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  • Miya Yamamoto,

    1. Mental Retardation Research Center, Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles
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  • Williams I. Rodriguez,

    1. Mental Retardation Research Center, Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles
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  • Jennifer Cheng,

    1. Mental Retardation Research Center, Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles
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  • Jimmy Tam,

    1. Mental Retardation Research Center, Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles
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  • Rosa P. Gomariz,

    1. Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
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  • Paul H. Patterson,

    1. Biology Division, California Institute of Technology, Pasadena
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  • James A. Waschek

    Corresponding author
    1. Mental Retardation Research Center, Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles
    • Department of Psychiatry, Mental Retardation Research Center, UCLA, Los Angeles, CA 90024-1759
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Abstract

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating peptide (PACAP) are induced strongly in neurons after several types of injury, and exhibit neuroprotective actions in vitro and in vivo. It is thought that changes in expression of neuropeptides and other molecules in injured neurons are mediated by new factors produced in Schwann and immune cells at the injury site, a loss of target-derived factors, or a combination of mediators. To begin to determine the role of the inflammatory mediators, we investigated axotomy-induced changes in VIP and PACAP gene expression in the facial motor nucleus in severe combined immunodeficient (SCID) mice, and in mice with targeted mutations in specific cytokine genes. In normal mice, VIP and PACAP mRNA was induced strongly in facial motor neurons 4 days after axotomy. The increase in PACAP mRNA was blocked selectively in SCID mice, indicating that mechanisms responsible for VIP and PACAP gene induction are not identical. The loss of PACAP gene expression in SCID mice after axotomy was fully reversed by an infusion of normal splenocytes, suggesting that PACAP mRNA induction requires inflammatory mediators. PACAP and VIP mRNA inductions, however, were maintained in mice lacking leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), and in mice lacking both receptors for tumor necrosis factor α (TNFα). The data suggest that an inflammatory response, most likely involving T lymphocytes, is necessary for the axotomy-induced increase in PACAP but not in VIP. LIF, IL-6, and TNFα, however, are not required for this response to injury. © 2003 Wiley-Liss, Inc.

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