Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction

Spinal cord injury and cyclophosphamide-induced cystitis dramatically alter lower urinary tract function and produce neurochemical, electrophysiologic al, and anatomical changes that may contribute to reorganization of the mic turition reflex. Mechanisms underlying this neural plasticity may involve a lterations in neurotrophic factors in the urinary bladder. These studies ha ve determined neurotrophic factors in the urinary bladder that may contribu te to reorganization of the micturition reflex following cystitis or spinal cord injury. A ribonuclease protection assay was used to measure changes i n urinary bladder neurotrophic factor mRNA (beta NGF, BDNF, GDNF, CNTF, NT- 3, and NT-4) following spinal cord injury (acute/chronic) or cyclophosphami de-induced cystitis (acute/chronic), The correlation between urinary bladde r nerve growth factor mRNA and nerve growth factor protein expression was a lso determined. Each experimental paradigm resulted in significant (P less than or equal to 0.05-0.005) changes in urinary bladder neurotrophic factor mRNA, although the magnitude of the changes differed between paradigms. Ur inary bladders from rats with acute spinal cord injury (4 days) exhibited t he largest increase in neurotrophic factor mRNA levels (beta NGF, al-fold i ncrease; BDNF, 78-fold increase; GDNF, Ii-fold increase; CNTF, 5.5-fold inc rease; NT-3, 10-fold increase; NT-4, 25-fold increase) relative to control urinary bladders, More modest but significant increases were demonstrated f or urinary bladders from rats with chronic (4-6 weeks) spinal cord injury. Significant increases in urinary bladder neurotrophic factor mRNA levels of comparable magnitude were demonstrated following either acute or chronic c yclophosphamide-induced cystitis. Increased abundance of urinary bladder ne rve growth factor mRNA was not always associated with increased total urina ry bladder nerve growth factor. Total urinary bladder nerve growth factor d ecreased following acute or chronic cystitis despite increased abundance of nerve growth factor mRNA. Urinary bladder nerve growth factor mRNA correla tes with protein measures 5-6 weeks following spinal cord injury but not ea rlier. The 5- to B-week time point coincided with the reemergence of the sp inal bladder-to-bladder reflex mechanisms following spinal cord injury. Dis crepancies between two measures (mRNA and protein) may reflect retrograde a xonal transport of nerve growth factor to the dorsal root ganglia (L6-S1). Retrogradely transported NGF may play a role in altered lower urinary tract function following spinal cord injury or cyclophosphamide-induced cystitis . (C) 2000 Academic Press.