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:
The journal of sexual medicine
影响因子:
--
通讯作者:
Podlasek CA
Podlasek CA
中科院分区:
其他
文献类型:
--
作者:
Bond CW;Angeloni N;Harrington D;Stupp S;Podlasek CA

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海绵体神经(CN)是常见的损伤过程中切除。神经微环境的操纵对于改善再生和开发新的勃起功能障碍(艾德)疗法至关重要。Sonic hedgehog(SHH)处理促进CN再生。这是如何发生的机制是未知的。脑源性神经营养因子(BDNF)促进CN损伤后勃起功能的恢复,并且已经表明在皮质神经元和坐骨神经中BDNF可能是SHH的靶点。确定SHH是否通过BDNF依赖性机制促进CN再生。通过Western定量PG/CN中的BDNF和胶质细胞酸性蛋白(GFAP),并使用t检验来确定差异。Sprague道利大鼠进行:1.双侧CN挤压(n=15),2. SHH治疗PG/CN(n=10),3. PG/CN中的SHH抑制(n=14只大鼠),4.用SHH处理PG/CN的CN挤压(n=10只大鼠),5. CN挤压与SHH治疗和BDNF抑制(n=14只大鼠),和6。CN损伤和SHH治疗阴茎(n=23)。在正常大鼠中,PG/CN中的SHH抑制使BDNF降低34%,而SHH处理使BDNF增加36%。BDNF增加了44%,响应SHH处理的破碎的CNs,和抑制BDNF的SHH蛋白处理的破碎的CNs阻碍再生。SHH调节正常和再生PG/CN中的BDNF。BDNF是SHH如何促进再生的机制的一部分,从而提供了一个机会,以进一步操纵神经微环境与联合治疗,以促进再生。
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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