Changes in Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Receptor Tyrosine Kinases (Trk) in Micturition Reflexes after Cyclophosphamide (CYP)-induced Cystitis in Rat

Changes in urinary bladder NGF and BDNF mRNA occur after CYP-induced cystitis. The present studies have examined NGF and BDNF protein expression in bladder and TrkA and TrkB, specific receptors for NGF and BDNF, expression in postganglionic neurons located in the major pelvic ganglia (MPG). Bladder and MPG BDNF and NGF expression were determined after acute (150 mg/kg, i.p., 4 and 48 hr) or chronic (75 mg/kg, i.p., every 3rd day for 7-10 days) CYP-induced cystitis using ELISA. Immunostaining was used to detect TrkA- and TrkB-immunoreactivity (IR) in MPG. Acute (4 and 48 hr) and chronic CYP-induced cystitis decreased bladder NGF (8-11-fold; p ≤ 0.001) and BDNF (3-16-fold; p ≤ 0.01) expression compared to that in control bladder. In control MPG, TrkA- and TrkB-IR cell profiles were observed throughout the MPG. Acute (4 hr) CYP-induced cystitis increased TrkA-(2-fold) and TrkB-IR (3-fold) in MPG cells compared to control MPG. Decreased bladder NGF and BDNF expression with acute or chronic CYP-induced cystitis may be due to retrograde transport of neurotrophic factor from bladder to MPG and/or dorsal root ganglia (DRG). Increased TrkA- and TrkB-IR may be induced by increased availability of NGF and BDNF in the MPG after cystitis. Because the terminals of postganglionic neurons terminate in the inflamed bladder and MPG cells express Trk receptors, these cells may be affected by changes in bladder neurotrophic factors. Changes in MPG cells as well as DRG cells may contribute to urinary bladder hyper-reflexia after CYP-induced cystitis.