Fox C M, Gash D M, Smoot M K, Cass W A
Department of Anatomy and Neurobiology, MN 225 Chandler Medical Center, University of Kentucky, Lexington 40536-0298, USA.
Brain Res. 2001 Mar 30;896(1-2):56-63. doi: 10.1016/s0006-8993(00)03270-4.
In young adult rats, glial cell line-derived neurotrophic factor (GDNF) can completely protect against 6-hydroxydopamine-induced loss of nigral dopamine neurons when administered 6 h prior to the 6-hydroxydopamine. The present study was undertaken to determine if GDNF would provide similar protective effects in aged rats. Male, Fischer 344 x Brown Norway hybrid rats of 3, 18 and 24 months of age were given an intranigral injection of GDNF or vehicle followed 6 h later with an intranigral injection of 6-hydroxydopamine. Nigral dopamine neuron cell survival, and striatal and nigral dopamine and DOPAC levels, were evaluated 2 weeks after the lesions. In vehicle treated animals cell survival on the lesioned side ranged from 15 to 27%. GDNF promoted significant cell survival in the nigra of all three age groups; however, the percent survival was lowest in the 24-month-old animals (85% at 3 months, 75% at 18 months, 56% at 24 months). Similarly, dopamine levels in the striatum and substantia nigra on the lesioned side remained significantly greater in the GDNF treated animals compared to the vehicle treated animals. As with the cell survival experiment, the protective effects of GDNF on dopamine levels were less in the 24-month-old animals. GDNF pretreatment also protected against 6-hydroxydopamine-induced reductions in striatal DOPAC levels in all age groups. Overall, these results indicate that GDNF can protect nigrostriatal dopamine neurons against the effects of 6-hydroxydopamine in aged as well as young adult rats. However, the extent of protection is less in the aged (24-month-old) animals.
在年轻成年大鼠中，胶质细胞系源性神经营养因子（GDNF）在6-羟基多巴胺给药前6小时给予时，可完全保护黑质多巴胺能神经元免受6-羟基多巴胺诱导的损失。本研究旨在确定GDNF在老年大鼠中是否具有类似的保护作用。对3、18和24月龄的雄性Fischer 344×Brown Norway杂交大鼠进行黑质内注射GDNF或赋形剂，6小时后再进行黑质内注射6-羟基多巴胺。在损伤后2周评估黑质多巴胺能神经元细胞存活情况，以及纹状体、黑质中的多巴胺和3,4-二羟基苯乙酸（DOPAC）水平。在接受赋形剂治疗的动物中，损伤侧的细胞存活率为15%至27%。GDNF促进了所有三个年龄组黑质中细胞的显著存活；然而，24月龄动物的存活率最低（3月龄时为85%，18月龄时为75%，24月龄时为56%）。同样，与接受赋形剂治疗的动物相比，接受GDNF治疗的动物损伤侧纹状体和黑质中的多巴胺水平仍显著更高。与细胞存活实验一样，GDNF对多巴胺水平的保护作用在24月龄动物中较小。GDNF预处理还可防止所有年龄组中6-羟基多巴胺诱导的纹状体DOPAC水平降低。总体而言，这些结果表明，GDNF可以保护黑质纹状体多巴胺能神经元免受6-羟基多巴胺在老年和年轻成年大鼠中的影响。然而，老年（24月龄）动物的保护程度较低。
