Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA.
Neurochem Int. 2010 Nov;57(5):540-6. doi: 10.1016/j.neuint.2010.06.019. Epub 2010 Jul 6.
Neurturin (NTN), a member of the glial cell line-derived neurotrophic factor (GDNF) family, has substantial effects on normal and lesioned nigrostriatal dopamine systems. However, its ability to protect against toxin-induced loss of striatal dopamine release has not been previously reported. The goal of the present study was to determine if NTN could protect against 6-hydroxydopamine (6-OHDA)-induced reductions in striatal dopamine overflow and tissue levels of dopamine and to compare the effects of NTN with those of GDNF. Male Fischer-344 rats were given a single injection of vehicle, or 5 microg NTN or GDNF, into the right striatum. The following day the animals were given a single injection of 12 microg 6-OHDA into the striatum at the same site where the trophic factor was injected. Microdialysis experiments conducted three weeks later indicated that the 6-OHDA decreased basal levels of dopamine and metabolites in the lesioned striatum compared to the contralateral striatum, and NTN was able to partially protect against the 6-OHDA-induced reductions. Injection of NTN one day prior to 6-OHDA also led to significant protection against loss of both potassium- and amphetamine-evoked overflow of dopamine. The NTN treatments partially protected against 6-OHDA-induced reductions in striatal tissue levels of dopamine and completely protected against loss of nigral dopamine content. The protective effects of NTN were similar in magnitude to those of GDNF. These results support that within the experimental parameters used in this study, NTN is as effective as GDNF in protecting against the dopamine-depleting effects of intrastriatal 6-OHDA.
神经营养因子（NTN）是胶质细胞源性神经营养因子（GDNF）家族的一员，对正常和损伤的黑质纹状体多巴胺系统有显著影响。然而，它是否能防止毒素引起的纹状体多巴胺释放损失尚未有报道。本研究的目的是确定 NTN 是否能防止 6-羟多巴胺（6-OHDA）引起的纹状体多巴胺溢出和组织多巴胺水平的降低，并将 NTN 的作用与 GDNF 的作用进行比较。雄性 Fischer-344 大鼠被给予单次右纹状体注射载体、5μg NTN 或 GDNF。次日，在同一部位给予 12μg 6-OHDA 注射到纹状体。三周后进行的微透析实验表明，6-OHDA 使损伤纹状体的多巴胺和代谢物的基础水平与对侧纹状体相比降低，而 NTN 能够部分防止 6-OHDA 引起的降低。在 6-OHDA 之前一天注射 NTN 也导致对钾和安非他命诱导的多巴胺溢出的损失有显著的保护作用。NTN 处理部分防止了 6-OHDA 引起的纹状体组织多巴胺水平的降低，并完全防止了黑质多巴胺含量的损失。NTN 的保护作用与 GDNF 的保护作用相当。这些结果支持在本研究中使用的实验参数内，NTN 在防止纹状体内 6-OHDA 引起的多巴胺耗竭效应方面与 GDNF 一样有效。
