p75NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide-induced cystitis

Authors

  • Mary Beth Klinger,

    1. Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405
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  • Beatrice Girard,

    1. Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405
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  • Margaret A. Vizzard

    Corresponding author
    1. Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405
    2. Department of Neurology, University of Vermont College of Medicine, Burlington, Vermont 05405
    • University of Vermont College of Medicine, Department of Neurology, D415A Given Research Building, Burlington, VT 05405
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Abstract

A role for nerve growth factor (NGF) in contributing to increased voiding frequency and altered sensation from the urinary bladder has been suggested. Previous studies have examined the expression and regulation of tyrosine kinase receptors (Trks) in micturition reflexes with urinary bladder inflammation. The present studies examine the expression and regulation of another receptor known to bind NGF, p75NTR, after various durations of bladder inflammation induced by cyclophosphamide (CYP). CYP-induced cystitis increased (P ≤ 0.001) p75NTR expression in the superficial lateral and medial dorsal horn in L1–L2 and L6–S1 spinal segments. The number of p75NTR-immunoreactive (-IR) cells in the lumbosacral dorsal root ganglia (DRG) also increased (P ≤ 0.05) with CYP-induced cystitis (acute, intermediate, and chronic). Quantitative, real-time polymerase chain reaction also demonstrated significant increases (P ≤ 0.01) in p75NTR mRNA in DRG with intermediate and chronic CYP-induced cystitis. Retrograde dye-tracing techniques with Fastblue were used to identify presumptive bladder afferent cells in the lumbosacral DRG. In bladder afferent cells in DRG, p75NTR-IR was also increased (P ≤ 0.01) with cystitis. In addition to increases in p75NTR-IR in DRG cell bodies, increases (P ≤ 0.001) in pericellular (encircling DRG cells) p75NTR-IR in DRG also increased. Confocal analyses demonstrated that pericellular p75NTR-IR was not colocalized with the glial marker, glial fibrillary acidic protein (GFAP). These studies demonstrate that p75NTR expression in micturition reflexes is present constitutively and modified by bladder inflammation. The functional significance of p75NTR expression in micturition reflexes remains to be determined. J. Comp. Neurol. 507:1379–1392, 2008. © 2008 Wiley-Liss, Inc.

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