Sonic Hedgehog Regulates Brain-Derived Neurotrophic Factor in Normal and Regenerating Cavernous Nerves

Christopher W. Bond, Nicholas Angeloni, Daniel Harrington, Samuel I Stupp, Carol A. Podlasek

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)730-737
Number of pages8
JournalJournal of Sexual Medicine
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Hedgehogs
Brain-Derived Neurotrophic Factor
Ganglia
Nerve Crush
Regeneration
Nerve Regeneration
Hedgehog Proteins
Glial Fibrillary Acidic Protein
Penis
Wounds and Injuries
Erectile Dysfunction
Sciatic Nerve
Prostatectomy
Sprague Dawley Rats

Keywords

  • BDNF
  • Cavernous Nerve
  • Erectile Dysfunction
  • Regeneration
  • Sonic Hedgehog

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Sonic Hedgehog Regulates Brain-Derived Neurotrophic Factor in Normal and Regenerating Cavernous Nerves. / Bond, Christopher W.; Angeloni, Nicholas; Harrington, Daniel; Stupp, Samuel I; Podlasek, Carol A.

In: Journal of Sexual Medicine, Vol. 10, No. 3, 03.2013, p. 730-737.

Research output: Contribution to journalArticle

Bond, Christopher W. ; Angeloni, Nicholas ; Harrington, Daniel ; Stupp, Samuel I ; Podlasek, Carol A. / Sonic Hedgehog Regulates Brain-Derived Neurotrophic Factor in Normal and Regenerating Cavernous Nerves. In: Journal of Sexual Medicine. 2013 ; Vol. 10, No. 3. pp. 730-737.
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abstract = "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.",
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T1 - Sonic Hedgehog Regulates Brain-Derived Neurotrophic Factor in Normal and Regenerating Cavernous Nerves

AU - Bond, Christopher W.

AU - Angeloni, Nicholas

AU - Harrington, Daniel

AU - Stupp, Samuel I

AU - Podlasek, Carol A.

PY - 2013/3

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N2 - 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.

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.

KW - BDNF

KW - Cavernous Nerve

KW - Erectile Dysfunction

KW - Regeneration

KW - Sonic Hedgehog

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