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Lymphocyte Regulation of Neuropeptide Gene Expression After Neuronal Injury

Armstrong, Brian D. and Hu, Zhongting and Abad, Catalina and Yamamoto, Miya and Rodriguez, Williams I. and Cheng, Jennifer and Tam, Jimmy and Gomariz, Rosa P. and Patterson, Paul H. and Waschek, James A. (2003) Lymphocyte Regulation of Neuropeptide Gene Expression After Neuronal Injury. Journal of Neuroscience Research, 74 (2). pp. 240-247. ISSN 0360-4012. doi:10.1002/jnr.10750.

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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.

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Additional Information:© 2003 Wiley-Liss, Inc. Received 10 June 2003; Accepted 20 June 2003. Contract grant sponsor: National Institutes of Health; Contract grant number: HD06576, HD04612; Contract grant sponsor: Norman Cousins Center for Psychoneuroimmunology; Contract grant sponsor: Roman Reed Spinal Cord Injury Research Fund of California. We thank S. Chhith for help in quantifying hybridization-positive neurons.
Funding AgencyGrant Number
Norman Cousins Center for PsychoneuroimmunologyUNSPECIFIED
Roman Reed Spinal Cord Injury Research Fund of CaliforniaUNSPECIFIED
Subject Keywords:VIP; PACAP; SCID; facial; axotomy; injury; SCID; LIF; interleukin-6, tumor necrosis factor; TNF
Issue or Number:2
Record Number:CaltechAUTHORS:20160216-122120555
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Official Citation:Armstrong, B. D., Hu, Z., Abad, C., Yamamoto, M., Rodriguez, W. I., Cheng, J., Tam, J., Gomariz, R. P., Patterson, P. H. and Waschek, J. A. (2003), Lymphocyte regulation of neuropeptide gene expression after neuronal injury. J. Neurosci. Res., 74: 240–247. doi: 10.1002/jnr.10750
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64508
Deposited By: Ruth Sustaita
Deposited On:17 Feb 2016 18:01
Last Modified:10 Nov 2021 23:31

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