PMID- 23237228
OWN - NLM
STAT- MEDLINE
DCOM- 20130919
LR  - 20220317
IS  - 1743-6109 (Electronic)
IS  - 1743-6095 (Print)
IS  - 1743-6095 (Linking)
VI  - 10
IP  - 3
DP  - 2013 Mar
TI  - Sonic Hedgehog regulates brain-derived neurotrophic factor in normal and 
      regenerating cavernous nerves.
PG  - 730-7
LID - 10.1111/jsm.12030 [doi]
AB  - INTRODUCTION: The cavernous nerve (CN) is commonly injured during prostatectomy. 
      Manipulation of the nerve microenvironment is critical to improve regeneration 
      and develop novel erectile dysfunction therapies. Sonic hedgehog (SHH) treatment 
      promotes CN regeneration. The mechanism of how this occurs is unknown. 
      Brain-derived neurotrophic factor (BDNF) facilitates return of erectile function 
      after CN injury and it has been suggested in cortical neurons and the sciatic 
      nerve that BDNF may be a target of SHH. AIM: To determine if SHH promotes CN 
      regeneration through a BDNF-dependent mechanism. METHODS: Sprague Dawley rats 
      underwent (i) bilateral CN crush (N = 15); (ii) SHH treatment of pelvic ganglia 
      (PG)/CN (N = 10); (iii) SHH inhibition in PG/CN (N = 14 rats); (iv) CN crush with 
      SHH treatment of PG/CN (N = 10 rats); (v) CN crush with SHH treatment and BDNF 
      inhibition (N = 14 rats); and (vi) CN injury and SHH treatment of the penis (N = 
      23). MAIN OUTCOME MEASURES: BDNF and glial fibrillary acidic protein were 
      quantified in PG/CN by Western, and a t-test was used to determine differences. 
      RESULTS: In normal rats SHH inhibition in the PG/CN decreased BDNF 34% and SHH 
      treatment increased BDNF 36%. BDNF was increased 44% in response to SHH treatment 
      of crushed CNs, and inhibition of BDNF in crushed CNs treated with SHH protein 
      hampers regeneration. CONCLUSIONS: SHH regulates BDNF in the normal and 
      regenerating PG/CN. BDNF is part of the mechanism of how SHH promotes 
      regeneration, thus providing an opportunity to further manipulate the nerve 
      microenvironment with combination therapy to enhance regeneration.
CI  - (c) 2012 International Society for Sexual Medicine.
FAU - Bond, Christopher W
AU  - Bond CW
AD  - Department of Urology, Northwestern University, Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Angeloni, Nicholas
AU  - Angeloni N
FAU - Harrington, Daniel
AU  - Harrington D
FAU - Stupp, Samuel
AU  - Stupp S
FAU - Podlasek, Carol A
AU  - Podlasek CA
LA  - eng
GR  - R01 DK079184/DK/NIDDK NIH HHS/United States
GR  - DK079184/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121213
PL  - Netherlands
TA  - J Sex Med
JT  - The journal of sexual medicine
JID - 101230693
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Shh protein, rat)
RN  - 97161-97-2 (staurosporine aglycone)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*metabolism
MH  - Carbazoles/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Hedgehog Proteins/antagonists & inhibitors/*pharmacology
MH  - Immunohistochemistry
MH  - Indole Alkaloids/pharmacology
MH  - Male
MH  - Nerve Regeneration/*drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Penis/*innervation
MH  - Peripheral Nerve Injuries
MH  - Peripheral Nerves/*physiology
MH  - Rats
PMC - PMC3593960
MID - NIHMS419137
EDAT- 2012/12/15 06:00
MHDA- 2013/09/21 06:00
PMCR- 2014/03/01
CRDT- 2012/12/15 06:00
PHST- 2012/12/15 06:00 [entrez]
PHST- 2012/12/15 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - S1743-6095(15)30283-6 [pii]
AID - 10.1111/jsm.12030 [doi]
PST - ppublish
SO  - J Sex Med. 2013 Mar;10(3):730-7. doi: 10.1111/jsm.12030. Epub 2012 Dec 13.