Neuroprotective effects of GDNF against 6-OHDA in young and aged rats
Neuroprotective effects of GDNF against 6-OHDA in young and aged rats
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DOI：
10.1016/s0006-8993(00)03270-4
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发表时间：
2001-03-30
期刊：
影响因子：
2.9
通讯作者：
Cass, WA
中科院分区：
文献类型：
--
作者：
Fox, CM;Gash, DM;Cass, WA
在幼年大鼠中，胶质细胞源性神经营养因子(GDNF)可完全对抗6-羟基多巴胺所致的黑质多巴胺神经元的丢失。本研究旨在确定GDNF是否会在老年大鼠中提供类似的保护作用。选用3月龄、18月龄和24月龄雄性、Fischer 344×Brown挪威杂交大鼠，分别在黑质内注射GDNF或赋形剂，6h后黑质内注射6-羟基多巴胺。损伤后2周观察黑质多巴胺神经元存活情况，以及纹状体和黑质多巴胺和DOPAC水平。在赋形剂处理的动物中，损伤侧的细胞存活率从15%到27%不等。GDNF显著促进了三个年龄组黑质细胞的存活；然而，24月龄动物的存活率最低(3月龄为85%，18月龄为75%，24月龄为56%)。同样，与赋形剂治疗的动物相比，GDNF治疗的动物患侧纹状体和黑质中的多巴胺水平仍然显著更高。与细胞存活实验一样，GDNF对24个月大的动物的多巴胺水平的保护作用较小。在所有年龄组中，GDNF预处理也可防止6-羟基多巴胺引起的纹状体DOPAC水平下降。总体而言，这些结果表明，GDNF可以保护黑质纹状体多巴胺神经元免受6-羟基多巴胺对老年和年轻成年大鼠的影响。然而，在老年(24个月大)的动物中，保护的程度较小。(C)2001 Elsevier Science B.V.保留所有权利。
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. (C) 2001 Elsevier Science B.V. All rights reserved.