The effect of intrastriatal single injection of GDNF on the nigrostriatal dopaminergic system in hemiparkinsonian rats: behavioral and histological studies using two different dosages
The effect of intrastriatal single injection of GDNF on the nigrostriatal dopaminergic system in hemiparkinsonian rats: behavioral and histological studies using two different dosages
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DOI：
10.1016/s0168-0102(00)00097-3
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发表时间：
2000-04-01
影响因子：
2.9
通讯作者：
Ohmoto, T
中科院分区：
文献类型：
--
作者：
Aoi, M;Date, I;Ohmoto, T
胶质细胞源性神经营养因子（GDNF）是转化生长因子β超家族的成员，是黑质纹状体多巴胺（DA）系统的神经营养因子。虽然先前的研究表明GDNF预处理可以预防DA神经毒素6-羟基多巴胺（6-OHDA）引起的黑质纹状体DA系统的退行性改变，但GDNF是否能诱导6-OHDA部分损伤后黑质纹状体DA系统的恢复尚不清楚。通常选择黑质作为GDNF的注射部位，但有限数量的研究使用纹状体作为通常进行神经移植的注射部位。在Sprague-Dawley大鼠中进行6-OHDA的单侧纹状体内给药以产生黑质纹状体DA系统的部分损伤。这些偏侧帕金森病模型大鼠在6-OHDA治疗后4周接受10或100 μ g单次注射人重组GDNF到纹状体的相同部分。接受10或100 μ g GDNF单次注射的两种动物在注射后2周表现出阿扑吗啡诱导的旋转减少。在接受100 μ g GDNF的动物中观察到比接受10 μ g GDNF的动物更有效和更长的功能恢复。酪氨酸羟化酶（TH）免疫细胞化学显示，TH阳性DA纤维密度在纹状体和DA细胞体的数量在黑质中接受10或100微克GDNF的动物比那些接受盐水。这些免疫细胞化学结果还表明，100 μ g GDNF比10 μ g GDNF更有效。这些形态和功能结果表明，GDNF治疗后4周6-OHDA损毁黑质纹状体DA系统可以诱导恢复。纹状体是偏侧帕金森病大鼠GDNF给药的良好部位，单次注射100 μ g GDNF比10 μ g GDNF更有效。(C)2000年由Elsevier Science爱尔兰有限公司和日本神经科学学会出版。All rights reserved.
Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopamine (DA) system. Although previous studies have shown that pretreatment with GDNF could prevent degenerative changes of nigrostriatal DA system by DA neurotoxin 6-hydroxydopamine (6-OHDA), it is not really known whether GDNF can induce recovery of nigrostriatal DA system after partial lesioning by 6-OHDA. Substantia nigra has been commonly chosen as injection site for GDNF but a limited number of studies have used striatum as injection site where neural transplantation is commonly performed. Unilateral intrastriatal administration of 6-OHDA was performed in Sprague-Dawley rats to create partial lesion of the nigrostriatal DA system. These hemiparkinsonian model rats received a 10-or 100-mu g single injection of human recombinant GDNF into the same portion of the striatum 4 weeks after 6-OHDA treatment. Both animals that received a 10- or 100-mu g single injection of GDNF showed decreased apomorphine-induced rotation at 2 weeks after injection. More potent and prolonged functional recovery was observed in animals receiving 100 mu g of GDNF than in those receiving 10 mu g of GDNF. Tyrosine hydroxylase (TH) immunocytochemistry revealed that TH positive DA fiber density in the striatum and the number of DA cell bodies in the substantia nigra were greater in animals receiving 10 or 100 mu g of GDNF than those receiving saline. These immunocytochemical results have also shown that 100 mu g of GDNF was more potent than 10 mu g of GDNF. These morphological and functional results indicate that GDNF treatment 4 weeks after 6-OHDA lesioning could induce recovery of nigrostriatal DA system. Striatum was a good site for GDNF administration for hemiparkinsonian rats and a single injection of 100 mu g of GDNF was more potent than 10 mu g of GDNF. (C) 2000 Published by Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.