Rosenberg L J, Lucas J H
Department of Physiology, Ohio State University, Columbus 43210, USA.
Brain Res. 1997 Nov 14;775(1-2):209-13. doi: 10.1016/s0006-8993(97)00954-2.
Ciliary neurotrophic factor (CNTF) has been found to increase neuronal survival during development and after axotomy. The present study tested the effects of CNTF on lesioned and uninjured mouse spinal cord (SC) neurons grown in tissue culture. An initial toxicity study found that a 24-72 h exposure of SC cultures to concentrations of CNTF above 1000 ng/ml caused stress and death of unlesioned neurons and glia. Pre-selected SC neurons were then subjected to transection of a primary dendrite 100 microns from the edge of the perikaryon (approximately 50% average survival at 24 h). Application of CNTF at concentrations ranging from 0.5 to 1000 ng/ml immediately after lesioning had no statistically significant effects on SC neuron survival 24 h after dendrotomy. Separation of control (no CNTF) and CNTF-treated cells into groups of putative alpha-motor (multipolar with somal diameters > or = 25 microns) and non-alpha-motor neurons (< 25 microns somal diameters) also failed to reveal any significant differences in survival. The lack of protection by CNTF of lesioned SC neurons in mature (21-28 DIV) cultures may reflect a loss of sensitivity to CNTF that occurs with development. Alternatively, protection by CNTF may require co-factors or factors that are released from target or other cells after injury but that are not present in SC cultures.
睫状神经营养因子(CNTF)已被发现在发育过程中和轴突切断后可增加神经元的存活。本研究测试了CNTF对组织培养中生长的损伤和未损伤小鼠脊髓(SC)神经元的影响。一项初步毒性研究发现,将SC培养物暴露于浓度高于1000 ng/ml的CNTF中24 - 72小时会导致未损伤的神经元和神经胶质细胞应激和死亡。然后对预先选择的SC神经元进行离体细胞手术,将其一个主要树突从核周边缘切断100微米(24小时时平均存活率约为50%)。损伤后立即应用浓度范围为0.5至1000 ng/ml的CNTF对树突切断术后24小时的SC神经元存活没有统计学上的显著影响。将对照(无CNTF)和经CNTF处理的细胞分为假定的α运动神经元(体细胞直径≥25微米的多极神经元)和非α运动神经元(体细胞直径<25微米)组,也未发现存活方面有任何显著差异。在成熟(21 - 28天体外培养)培养物中,CNTF对损伤的SC神经元缺乏保护作用,这可能反映了随着发育对CNTF的敏感性丧失。或者,CNTF的保护作用可能需要共因子或损伤后从靶细胞或其他细胞释放但在SC培养物中不存在的因子。