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.
OBJECTIVE
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.
Bella
Anthony J
AJ
Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA 94143-0738, USA. abella@urology.ucsf.edu
Lin
Guiting
G
Garcia
Maurice M
MM
Tantiwongse
Kavirach
K
Brant
William O
WO
Lin
Ching-Shwun
CS
Lue
Tom F
TF
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005726:Ganglia, Parasympathetic / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D053613:Janus Kinase 1; D053612:Janus Kinases / Q000378:metabolism*; D008297:Male; D010413:Penis / Q000294:innervation* / Q000378:metabolism* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D050791:STAT Transcription Factors; C507906:Jak1 protein, rat; D053613:Janus Kinase 1; D053612:Janus Kinases