Differential changes in brain-derived neurotrophic factor and extracellular signal-regulated kinase in rat primary afferent pathways with colitis

Authors

  • L.-y. Qiao,

    1. Department of Physiology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
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  • M. A. Gulick,

    1. Department of Physiology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
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    • 1

      These authors contributed equally to this study.

  • J. Bowers,

    1. Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
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    • 1

      These authors contributed equally to this study.

  • J. F. Kuemmerle,

    1. Department of Physiology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
    2. Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
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  • J. R. Grider

    1. Department of Physiology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
    2. Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
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Li-Ya Qiao, PhD, Department of Physiology, School of Medicine, Virginia Commonwealth University, PO Box 980551, Richmond, VA 23298-0551, USA.
Tel: +1 (804) 828-8504; fax: +1 (804) 828-2500; e-mail: lqiao2@vcu.edu

Abstract

Abstract  Brain-derived neurotrophic factor (BDNF) has been postulated to participate in inflammation-induced visceral hypersensitivity by modulating the sensitivity of visceral afferents through the activation of intracellular signalling pathways such as the extracellular signal-regulated kinase (ERK) pathway. In the current study, we assessed the expression levels of BDNF and phospho-ERK in lumbosacral dorsal root ganglia (DRG) and spinal cord before and during tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in rats with real-time PCR, ELISA, western blot and immunohistochemical techniques. BDNF mRNA and protein levels were increased in L1 and S1 but not L6 DRG when compared with control (L1: two- to five-fold increases, P < 0.05; S1: two- to three-fold increases, P < 0.05); however, BDNF protein but not mRNA level was increased in L1 and S1 spinal cord when compared with control. In parallel, TNBS colitis significantly induced phospho-ERK1/2 expression in L1 (four- to five-fold, P < 0.05) and S1 (two- to three-fold, P < 0.05) but not in L6 spinal cord levels. Immunohistochemistry results showed that the increase in phospho-ERK1/2 expression occurred at the region of the superficial dorsal horn and grey commisure of the spinal cord. In contrast, there was no change in phospho-ERK5 in any level of the spinal cord examined during colitis. The regional and time-specific changes in the levels of BDNF mRNA, protein and phospho-ERK with colitis may be a result of increased transcription of BDNF in DRG and anterograde transport of BDNF from DRG to spinal cord where it activates intracellular signalling molecules such as ERK1/2.

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