Emerich Dwaine F, Thanos Christopher G, Sanberg Paul R
InCytu, Inc., Lincoln, Rhode Island 02865, USA.
Curr Aging Sci. 2008 Jul;1(2):105-11. doi: 10.2174/1874609810801020105.
The impact of intraventricular ciliary neurotrophic factor (CNTF) on motor function in aged rats was evaluated. Spontaneous locomotion and motor coordination were quantified in young (5-6 months) and aged (24-25 months) rats. Relative to young animals, aged rats were significantly less active, fell more rapidly from a rotating rod, and were unable to maintain their balance on a wooden beam. Aged animals received bilateral intraventricular implants of polymer-encapsulated fibroblasts that were genetically modified to secrete CNTF. Controls received either no implant or capsules loaded with mock transfected cells. One month after implantation the aged animals that received CNTF implants were significantly more active and were improved on the rotorod and beam balance tests. The improvement in performance on the rotorod and beam balance tests was dependant on the task difficulty and dissipated at higher rotations (rotorod) and smaller beam widths (beam balance). No recovery was seen in aged animals receiving control implants. Postmortem removal of the encapsulated cells confirmed that they continued to secrete CNTF. These data are the first to suggest that intracerebral delivery of CNTF might be useful for slowing or reversing age-related changes in motor function.
评估了脑室内睫状神经营养因子（CNTF）对老年大鼠运动功能的影响。对年轻（5 - 6个月）和老年（24 - 25个月）大鼠的自发运动和运动协调性进行了量化。与年轻动物相比，老年大鼠的活动明显减少，从旋转杆上掉落得更快，并且无法在木梁上保持平衡。老年动物接受了双侧脑室内植入聚合物包裹的成纤维细胞，这些细胞经过基因改造以分泌CNTF。对照组要么不植入，要么植入装有模拟转染细胞的胶囊。植入后一个月，接受CNTF植入的老年动物活动明显增加，并且在转棒试验和木梁平衡试验中表现有所改善。转棒试验和木梁平衡试验中性能的改善取决于任务难度，并且在较高转速（转棒试验）和较窄木梁宽度（木梁平衡试验）时消失。接受对照植入的老年动物未见恢复。对包裹细胞进行死后移除证实它们继续分泌CNTF。这些数据首次表明，脑内递送CNTF可能有助于减缓或逆转与年龄相关的运动功能变化。
