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

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. Bond CW, Angeloni N, Harrington D, Stupp S, and Podlasek CA. Sonic hedgehog regulates brain-derived neurotrophic factor in normal and regenerating cavernous nerves. J Sex Med 2013;10:730737.