Neuronal survival following remote adenovirus gene delivery
Neuronal survival following remote adenovirus gene delivery
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DOI：
10.3171/spi.2002.96.2.0212
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发表时间：
2002-03-01
影响因子：
4.1
通讯作者：
Feldman, EL
中科院分区：
文献类型：
--
作者：
Boulis, NM;Turner, DE;Feldman, EL
Object.病毒介导的中枢神经系统基因递送是治疗创伤组织或退行性疾病的有希望的手段。在本研究中，作者研究了基因表达和神经元的生存在脊髓后坐骨神经管理的腺病毒载体表达LacZ报告基因。方法，腺病毒基因表达的时间过程。在大鼠坐骨神经显微注射生理盐水或报告病毒后，通过对β-半乳糖苷酶（β-Gal）、末端脱氧核苷酸转移酶和甲酚紫染色，定量测定大鼠腰髓中的DNA片段和神经元密度。β-Gal的表达后远程hector交付，在7天达到峰值，此后下降，但不伴随神经元细胞死亡。通过DNA片段化来测量。在检查的任何时间点，在病毒处理的大鼠和对照大鼠之间检测到脊髓运动神经元密度没有显著差异。尽管在腺病毒注射前用环孢霉素处理的大鼠中取出的脊髓在第7天含有更多的β-Gal染色的神经元（占总神经元的67%），但染色神经元数量的减少并不被运动神经元密度的下降所抵消。作者得出结论，远程基因表达受到非细胞溶解过程的抑制。
Object. Virus-mediated central nervous system gene delivery is a promising means of treating traumatized tissue or degenerative diseases. In the present study, the authors examined gene expression and neuronal survival in the spinal cord after sciatic nerve administration of an adenovirus vector expressing a LacZ reporter gene.Method, The time course of adenovirus gene expression. DNA fragmentation, and neuronal density ere quantified in rat lumbar spinal cord by staining for beta-galactosidase (beta-Gal), terminal deoxynucleotidyl transferase, and cresyl violet after microinjection of either saline or the reporter virus into rat sciatic nerve. The expression of beta-Gal following remote hector delivery, peaked at 7 days and declined thereafter but was not accompanied by neuronal cell death. as measured by DNA fragmentation. No significant difference in spinal motor neuron density was detected between virus-treated and control rats at any time point examined. Although the,pinal cords removed from rats treated with cyclosporine prior to adenovirus injection contained substantially more neurons staining for beta-Gal at 7 days (67% of total neurons), the decay in the number of stained neurons was not paralleled by a decline in motor neuron density.Conclusions. The authors conclude that remote gene expression is suppressed by a noncytolytic process.