Sonic Hedgehog regulates brain-derived neurotrophic factor in normal and regenerating cavernous nerves.
Sonic Hedgehog regulates brain-derived neurotrophic factor in normal and regenerating cavernous nerves.
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DOI:
10.1111/jsm.12030
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发表时间:
2013-03
期刊:
影响因子:
--
通讯作者:
Podlasek CA
中科院分区:
文献类型:
--
作者:
Bond CW;Angeloni N;Harrington D;Stupp S;Podlasek CA
The cavernous nerve (CN) is commonly injured during prostatectomy. Manipulation of the nerve microenvironment is critical to improve regeneration and develop novel erectile dysfunction (ED) 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. To determine if SHH promotes CN regeneration through a BDNF dependent mechanism. BDNF and glial fibrillary acidic protein (GFAP) were quantified in PG/CN by Western and a t-test was used to determine differences. Sprague Dawley rats underwent: 1. Bilateral CN crush (n=15), 2. SHH treatment of PG/CN (n=10), 3. SHH inhibition in PG/CN (n=14 rats), 4. CN crush with SHH treatment of PG/CN (n=10 rats), 5. CN crush with SHH treatment and BDNF inhibition (n=14 rats), and 6. CN injury and SHH treatment of the penis (n=23). 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. 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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