RGD Reference Report - Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury. - Rat Genome Database
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Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury.

Authors: Angeloni, Nicholas  Bond, Christopher W  Harrington, Daniel  Stupp, Samuel  Podlasek, Carol A 
Citation: Angeloni N, etal., J Sex Med. 2013 May;10(5):1240-50. doi: 10.1111/j.1743-6109.2012.02930.x. Epub 2012 Sep 20.
RGD ID: 12879407
Pubmed: (View Article at PubMed) PMID:22994531
DOI: Full-text: DOI:10.1111/j.1743-6109.2012.02930.x


INTRODUCTION: The cavernous nerve (CN) is commonly injured during prostatectomy, resulting in erectile dysfunction (ED). Although peripheral nerves have a limited ability to regenerate, a return of function typically does not occur due to irreversible down stream morphological changes in the penis that result from CN injury. We have shown in previous studies that sonic hedgehog (SHH) is critical for CN regeneration and improves erectile function after crush injury.
AIMS: Examine a new direction, to determine if SHH is neuroprotective to the pelvic ganglia (PG)/CN after crush injury. A secondary focus is to examine if SHH signaling decreases with age in the PG/CN.
METHODS: Sprague-Dawley rats underwent bilateral CN crush and SHH and glial fibrillary acidic protein were quantified by western analysis of the PG/CN (N = 6 rats at each time point) at 1, 2, 4, 7, and 14 days, and the apoptotic index was measured in the penis. SHH was quantified by western in the PG/CN with blockade of anterograde transport (N = 4 rats) in comparison to mouse IgG (N = 4 rats). If SHH is neuroprotective was examined at 4 (N = 14 rats) and 7 days (N = 16 rats) of treatment after CN crush. SHH protein was quantified in aging (P200-300, N = 5 rats) PG/CN in comparison to normal adult (P115-120, N = 3 rats) PG/CN. Main Outcome Measures. SHH pathway was examined in PG via immunohistochemistry, in situ, western, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
RESULTS: SHH is neuroprotective in the PG/CN with injury. SHH localization in the PG/CN suggests SHH interaction in neuronal/glial signaling. SHH protein is significantly decreased in the PG/CN after crush injury and in the aged PG/CN. Signals from the PG are required to maintain SHH in the CN.
CONCLUSIONS: There is a window of opportunity immediately after nerve insult in which manipulation of SHH signaling in the nerve microenvironment can affect long-term regeneration outcome.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Shh  (sonic hedgehog signaling molecule)

Genes (Mus musculus)
Shh  (sonic hedgehog)

Genes (Homo sapiens)
SHH  (sonic hedgehog signaling molecule)


Additional Information