Kato R, Wolfe D, Coyle C H, Wechuck J B, Tyagi P, Tsukamoto T, Nelson J B, Glorioso J C, Chancellor M B, Yoshimura N
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Gene Ther. 2009 Jan;16(1):26-33. doi: 10.1038/gt.2008.132. Epub 2008 Jul 31.
Neurturin (NTN), a member of glial cell line-derived neurotrophic factor (GDNF) family, is known as an important neurotrophic factor for penis-projecting neurons. We recently demonstrated significant protection from erectile dysfunction (ED) following a replication-defective herpes simplex virus (HSV) vector-mediated GDNF delivery to the injured cavernous nerve. Herein, we applied HSV vector-mediated delivery of NTN to this ED model. Rat cavernous nerve was injured bilaterally using a clamp and dry ice. For HSV-treated groups, 20 microl of vector stock was administered directly to the damaged nerve. Delivery of an HSV vector expressing both green fluorescent protein and lacZ (HSV-LacZ) was used as a control. Intracavernous pressure along with systemic arterial pressure (ICP/AP) was measured 2 and 4 weeks after the nerve injury. Fluorogold (FG) was injected into the penile crus 7 days before being killed to assess neuronal survival. Four weeks after nerve injury, rats treated with HSV-NTN exhibited significantly higher ICP/AP compared with untreated or control vector-treated groups. The HSV-NTN group had more FG-positive major pelvic ganglion neurons than the control group following injury. HSV vector-mediated delivery of NTN could be a viable approach for the improvement of ED following cavernous nerve injury.
神经营养因子（NTN）是胶质细胞源性神经营养因子（GDNF）家族的成员之一，是一种对阴茎投射神经元起重要作用的神经营养因子。我们最近证明，在复制缺陷型单纯疱疹病毒（HSV）载体介导的GDNF传递至受损海绵体神经后，可显著预防勃起功能障碍（ED）。在此，我们将HSV载体介导的NTN传递应用于该ED模型。使用止血钳和干冰双侧损伤大鼠海绵体神经。对于HSV治疗组，将20微升载体原液直接注射至受损神经。以表达绿色荧光蛋白和LacZ的HSV载体（HSV-LacZ）传递作为对照。在神经损伤后2周和4周测量海绵体内压以及体动脉压（ICP/AP）。在处死前7天将荧光金（FG）注入阴茎脚以评估神经元存活情况。神经损伤后4周，与未治疗或对照载体治疗组相比，接受HSV-NTN治疗的大鼠表现出显著更高的ICP/AP。损伤后，HSV-NTN组比对照组有更多的FG阳性主要盆神经节神经元。HSV载体介导的NTN传递可能是改善海绵体神经损伤后ED的一种可行方法。
