Signaling pathways regulating BDNF expression in lumbosacral dorsal root ganglia during bladder inflammation

Neuronal mediators expressed by sensory neurons play significant roles in urinary bladder hyperactivity induced by bladder inflammation (cystitis). The present study examined changes in the expression level of brain‐derived neurotrophic factor (BDNF) in the lumbosacral L1 and L6 dorsal root ganglia (DRG) during cyclophosphamide (CYP)‐induced cystitis in male SD rats, and investigated the potential signaling pathways leading to these changes. Real‐time PCR showed that cystitis increased the expression levels of BDNF in L1 and L6 DRG by 1.5‐fold (p<0.05) 48 h post CYP injection. Western blot showed that the intracellular signal molecules Akt and ERK5, but not ERK1/2, were activated in these DRGs by cystitis; this suggests a possible involvement of nerve growth factor (NGF) retrograde signaling from the inflamed bladder to DRG during cystitis. This is consistent with the result that the level of NGF was increased in the inflamed bladder. To examine the possible role of retrograde transport of NGF in BDNF expression in DRG, the L6 ganglia‐nerve preparation was cultured in a two‐compartmented chamber, and the axonal terminals were treated with NGF (100 ng/mL) for 3 h which significantly increased BDNF expression in the neuronal soma by 15‐fold. These results suggest that cystitis‐induced NGF expression in the inflamed urinary bladder might have a role in the BDNF up‐regulation in DRG during cystitis. NIH DK 077917 to LYQ