Temporal changes in neurotrophic factors and neurite outgrowth in the major pelvic ganglion following cavernous nerve injury.

Temporal changes in neurotrophic factors and neurite outgrowth in the major pelvic ganglion following cavernous nerve injury.
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DOI:
10.1002/jnr.23553
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发表时间:
2015-06
影响因子:
4.2
通讯作者:
Bivalacqua, Trinity J.
Bivalacqua, Trinity J.
中科院分区:
医学3区
文献类型:
--
作者:
Hannan, Johanna L.;Albersen, Maarten;Stopak, Bernard L.;Liu, Xiaopu;Burnett, Arthur L.;Hoke, Ahmet;Bivalacqua, Trinity J.

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尽管保留神经的根治性前列腺切除术,但神经损伤和勃起功能障碍(ED)普遍存在,预防神经退行性变非常重要。双侧海绵状神经损伤(BCNI)后大盆腔神经节(MPG)的神经营养因子和神经突生长特征。分别于术后2、7、14、21、30和60天(n=8/组)测量年轻雄性Sprague-Dawley大鼠海膜内压与平均动脉压比(ICP/MAP)。对神经胶质细胞系源性神经营养因子(GDNF)、神经生长因子(NGF)、神经turin (NRTN)、神经营养因子-3 (NT3)、神经营养因子-4 (NT4)、脑源性神经营养因子(BDNF)、血管内皮生长因子(VEGF)和激活转录因子3 (ATF3)进行MPG基因表达(qPCR)和Western blot检测。BCNI后24h、48h、3、7 d分别取损伤大鼠,取mpg (n=3/组)。mpg在基质中培养,并测量神经突生长情况。BCNI大鼠勃起功能早期受损,60天后改善。BCNI后MPGs中GDNF、NGF、BDNF和ATF3基因表达显著升高(48h-21d, p<0.05), NT3基因表达显著降低(p<0.05)。BCNI 48h时GDNF和NGF蛋白水平升高。BCNI后24h和48h MPG神经突生长均高于假手术组(分别为658±19μm、607±24μm、393±23μm, p<0.05)。进一步研究神经营养因子在调节信号通路中的作用可能为神经源性ED的治疗提供途径。
Despite nerve-sparing radical prostatectomy, nerve damage and erectile dysfunction (ED) prevails and preventing neurodegeneration is of great importance. Neurotrophic factors and neurite outgrowth were characterized in major pelvic ganglia (MPG) following bilateral cavernous nerve injury (BCNI). Young male Sprague-Dawley rats underwent sham or BCNI surgery and intracavernosal pressure to mean arterial pressure ratio (ICP/MAP) was measured 2, 7, 14, 21, 30 and 60 days following injury (n=8/group). MPG gene expression (qPCR) and Western blot was performed for glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurturin (NRTN), neurotrophin-3 (NT3), neurotrophin-4 (NT4), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and activating transcription factor 3 (ATF3). Additional rats were injured and MPGs removed 24h, 48h, 3 and 7 days following BCNI (n=3/group). MPGs were cultured in matrigel and neurite outgrowth measured. Erections were impaired early and improved by 60 days in BCNI rats. GDNF, NGF, BDNF and ATF3 gene expression was significantly increased and NT3 decreased in MPGs following BCNI (48h-21d; p<0.05). GDNF and NGF proteins levels were elevated in 48h BCNI. MPG neurite outgrowth from 24h and 48h BCNI was higher than sham (658±19μm; 607±24μm; 393±23μm, respectively, p<0.05). Further studies examining the roles of neurotrophic factors in modulating signaling pathways may provide therapeutic avenues for neurogenic-mediated ED.
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