Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat
Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat
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DOI：
10.1016/j.expneurol.2005.10.008
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
Mendell, LM
中科院分区：
文献类型：
--
作者：
Arvanian, VL;Bowers, WJ;Mendell, LM
我们研究了神经营养因子-3 （NT-3）和nmda - 2d表达单元是否能增强新生大鼠脊髓中的传递，从而增强受损新生脊髓中的突触连接。我们采用电生理方法评估挫伤和交错双半切脊髓损伤（SCI）模型中突触传递到单个运动神经元的强度。在出生后第2天（P2）进行胸椎尾侧水平（T11-T12）的脊髓损伤。将含有nt -3分泌成纤维细胞和表达nr2d的HSV-1扩增子（HSV-1扩增子）的桥塞植入病变上方。对照动物用扩增子表达β -半乳糖苷酶（HSVIac）处理。治疗8-10天后，处死大鼠，取脊髓进行细胞内记录。未处理的挫伤脊髓保留了部分白质，损伤区观察到弱的单突触反应。然而，在双半切损伤的控制索中未观察到突触连接。NT-3和HSVnr2d联合治疗可增强挫伤脊髓的单突触连接，并诱导双半反射脊髓出现弱但功能性的多突触连接。相比之下，单独使用NT-3或HSVnr2d治疗都不能通过半切区诱导突触反应的出现。这些结果表明，NT-3分泌成纤维细胞联合HSVnr2d治疗促进了NMDA受体的功能，增强了不完全性脊髓损伤后存活的连接，因此这种联合治疗可能促进脊髓损伤后功能的恢复。(c) 2005爱思唯尔公司版权所有。
We investigated whether administration of neurotrophin-3 (NT-3) and NMDA-2D-expressing units, found previously to enhance transmission in neonatal rat spinal cord, strengthens synaptic connections in the injured neonatal cord. We employed electrophysiological methods to evaluate the strength of synaptic transmission to individual motoneurons in the contusion and staggered double hemisection spinal cord injury (SCI) models. SCI at caudal thoracic levels (T11-T12) was carried out at postnatal day 2 (P2). Plugs containing NT-3-secreting fibroblasts and NR2D-expressing HSV-1 amplicons (HSVnr2d) were implanted above the lesion. Control animals were treated with an amplicon-expressing beta-galactosidase (HSVIac). After 8-10 days of treatment, the rats were sacrificed and spinal cords were removed for intracellular recording. Untreated contused cords preserved a fraction of white matter and weak monosynaptic responses were observed through the injury region. However, no synaptic connections were observed in control cords receiving double hemisection injury. Combined treatment with NT-3 and HSVnr2d strengthened monosynaptic connections in contused cords and induced the appearance of weak but functional multisynaptic connections in double hemilected cords. In contrast, treatment with either NT-3 or HSVnr2d alone failed to induce appearance of synaptic responses through the hemisected region. These results suggest that chronic treatment with NT-3 secreting fibroblasts combined with facilitated function of NMDA receptors by HSVnr2d treatment strengthens connections that survive incomplete SCI and therefore that such combined treatment might facilitate recovery of function following SCI. (c) 2005 Elsevier Inc. All rights reserved.