PMID- 16942527
OWN - NLM
STAT- MEDLINE
DCOM- 20061206
LR  - 20171016
IS  - 1743-6095 (Print)
IS  - 1743-6095 (Linking)
VI  - 3
IP  - 5
DP  - 2006 Sep
TI  - Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway 
      to promote neurite growth in the major pelvic ganglion of the rat: part 2.
PG  - 821-829
LID - S1743-6095(15)31399-0 [pii]
LID - 10.1111/j.1743-6109.2006.00292.x [doi]
AB  - INTRODUCTION: Surgical and radiation therapies of bladder and prostate cancers 
      may damage cavernous nerves and cause erectile dysfunction (ED). We previously 
      showed that brain-derived neurotrophic factor (BDNF) could restore erectile 
      function in a neurogenic ED rat model. We now investigated the signaling 
      mechanism of BDNF in major pelvic ganglia (MPG) explants. AIM: To identify the 
      signaling mechanism that mediates the neurotrophic effect of BDNF in cultured 
      MPG. METHODS: Major pelvic ganglia was isolated from male rats for 
      immunohistochemistry and immunofluorescence staining to locate BDNF receptors, 
      pan-neurotrophin 75 (p75), tropomyosin-related kinase B (TrkB), and 
      tropomyosin-related kinase C (TrkC). The dorso-caudal region of MPG was treated 
      with BDNF to determine the optimal dosage for promoting neurite growth. Specific 
      kinase inhibitors AG490, KT5720, LY294002, and U0126 were then used to treat MPG 
      either alone or prior to BDNF treatment. The treated MPG was examined for neurite 
      growth and for expression and phosphorylation of JAK2, STAT1, and STAT3 by 
      Western blot analysis. MAIN OUTCOME MEASURES: Lengths of neurite growth from MPG 
      were measured to quantify the effects of BDNF and to identify specific signaling 
      pathways. Ratios of phosphorylated vs. unphosphoryated proteins of JAK2, STAT1, 
      and STAT2 in control and treated MPG were determined to confirm JAK/STAT as the 
      principal signaling pathway. RESULTS: Tropomyosin-related kinase B and TrkC were 
      localized to neurons whereas p75 to perineuronal satellite glial cells (SGC). The 
      optimal dosage of BDNF for promoting MPG neurite growth was between 25 and 50 
      ng/mL. Among the four specific kinase inhibitors, AG490 was the strongest in 
      suppressing MPG neurite growth as well as BDNF-induced phosphorylation of JAK2, 
      STAT1, and STAT3. CONCLUSIONS: In rat MPG, TrkB and TrkC were expressed in 
      neurons, whereas p75 in SGC. Optimal BDNF dosage for promoting MPG neurite growth 
      was between 25 and 50 ng/mL. BDNF promotes MPG neurite growth primarily by 
      activating the JAK/STAT pathway.
FAU - Lin, Guiting
AU  - Lin G
AD  - Knuppe Molecular Urology, Laboratory, Department of Urology, School of Medicine, 
      University of California, San Francisco, CA, USA. Electronic address: 
      cslin@urology.ucsf.edu.
FAU - Bella, Anthony J
AU  - Bella AJ
AD  - Knuppe Molecular Urology, Laboratory, Department of Urology, School of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Lue, Tom F
AU  - Lue TF
AD  - Knuppe Molecular Urology, Laboratory, Department of Urology, School of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Lin, Ching-Shwun
AU  - Lin CS
AD  - Knuppe Molecular Urology, Laboratory, Department of Urology, School of Medicine, 
      University of California, San Francisco, CA, USA.
LA  - eng
GR  - 2R01-DK-45370/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Sex Med
JT  - The journal of sexual medicine
JID - 101230693
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (STAT Transcription Factors)
RN  - EC 2.7.10.2 (Jak1 protein, rat)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Chromatography, High Pressure Liquid/methods
MH  - Ganglia, Parasympathetic/*metabolism
MH  - In Vitro Techniques
MH  - Janus Kinase 1/*metabolism
MH  - Male
MH  - Neurites/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/*metabolism
MH  - STAT Transcription Factors/*metabolism
MH  - Signal Transduction
EDAT- 2006/09/01 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/09/01 09:00
PHST- 2006/09/01 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/09/01 09:00 [entrez]
AID - S1743-6095(15)31399-0 [pii]
AID - 10.1111/j.1743-6109.2006.00292.x [doi]
PST - ppublish
SO  - J Sex Med. 2006 Sep;3(5):821-829. doi: 10.1111/j.1743-6109.2006.00292.x.