Upregulation of penile brain-derived neurotrophic factor (BDNF) and activation of the JAK/STAT signalling pathway in the major pelvic ganglion of the rat after cavernous nerve transection.

OBJECTIVES: Increasing attention is being focused on identifying novel approaches to recover cavernous nerve (CN) function after injury or secondary to disease states such as diabetes mellitus. We examined penile brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) expression, and activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) molecular pathway in the major pelvic ganglion (MPG) after CN injury in the rat.
METHODS: Five groups of eight male Sprague-Dawley rats (4 mo, 250-300 g) were used in this study. The penis and MPG with attached CN segment were harvested at 0 h (controls), 12, and 24 h, as well as at 5 and 12 d after CN axotomy, for protein, messenger RNA (mRNA), and immunohistochemical analysis.
RESULTS: mRNA and protein expression of BDNF was upregulated in the penis after injury (p<0.05). Levels of NT-3 were unchanged. The JAK/STAT pathway was activated in the MPG after transection, as evidenced by increased STAT1 (peak: 24 h) and STAT3 (peak: 5 d) phosphorylation (p<0.01 vs. controls).
CONCLUSIONS: This study demonstrates increased expression of penile BDNF and upregulation of phosphorylated STAT1 and STAT3 in the MPG in response to CN transection. Activation of the JAK/STAT pathway after injury represents a promising new molecular target for modulating CN survival and regeneration.