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


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.
Murray
Elaine
E
Department of Neurology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Malley
Susan E
SE
Qiao
Li-Ya
LY
Hu
Vivian Y
VY
Vizzard
Margaret A
MA
D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D003520:Cyclophosphamide / Q000494:pharmacology; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000096:biosynthesis*; D020813:Receptor, trkB / Q000096:biosynthesis*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D003520:Cyclophosphamide; D020917:Receptor, trkA; D020813:Receptor, trkB