Cyclophosphamide induced cystitis alters neurotrophin and receptor tyrosine kinase expression in pelvic ganglia and bladder

J Urol. 2004 Dec;172(6 Pt 1):2434-9. doi: 10.1097/01.ju.0000143549.29867.4e.

Abstract

Purpose: We examined neurotrophin and receptor tyrosine kinase (Trk) expression in the bladder and major pelvic ganglia (MPG) after cyclophosphamide induced cystitis in rats.

Materials and methods: The bladder and MPG were used in immunohistochemical studies, enzyme-linked immunoassays and Western blots for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), TrkA and TrkB. Bladder postganglionic MPG cells were labeled by tracing techniques.

Results: NGF and BDNF expression was decreased in the bladder of all rats after cystitis (p < or =0.001). NGF and BDNF expression was increased in the MPG in male rats with cystitis (p < or =0.01). Cells expressing TrkA and TrkB immunoreactivity (IR) increased 78% to 81% in the MPG in male rats with cystitis. TrkA-IR or TrkB-IR bladder postganglionic cells increased 50% to 74% with cystitis. Cystitis increased TrkA-IR 5 to 10-fold and TrkB-IR 10 to 12-fold in detrusor muscle. TrkA-IR and TrkB-IR were prominent in control urothelium but decreased with cystitis. After cystitis TrkB-IR nerve fibers and TrkA-IR cellular infiltrates were more apparent compared to controls.

Conclusions: Cystitis decreases bladder NGF and BDNF expression, whereas MPG expression is increased. This change may reflect neurotrophin release at the bladder and retrograde transport to the MPG. TrkA-IR and TrkB-IR are increased in bladder postganglionic cells and bladders with cystitis. This increase may reflect a shift in Trk staining from urothelium to detrusor muscle and nerve fibers with cystitis. Neurotrophin/Trk interactions in the bladder and MPG may contribute to bladder overactivity with cystitis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autonomic Fibers, Postganglionic / drug effects*
  • Autonomic Fibers, Postganglionic / metabolism*
  • Brain-Derived Neurotrophic Factor / biosynthesis*
  • Cyclophosphamide / pharmacology
  • Cystitis / chemically induced
  • Cystitis / metabolism*
  • Female
  • Male
  • Nerve Growth Factors / biosynthesis*
  • Rats
  • Rats, Wistar
  • Receptor, trkA / biosynthesis*
  • Receptor, trkB / biosynthesis*
  • Urinary Bladder / drug effects*
  • Urinary Bladder / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Cyclophosphamide
  • Receptor, trkA
  • Receptor, trkB