l-Dopa-induced reversal in striatal glutamate following partial depletion of nigrostriatal dopamine with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
l-Dopa-induced reversal in striatal glutamate following partial depletion of nigrostriatal dopamine with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
复制标题
DOI：
10.1016/j.neuroscience.2005.08.003
复制
发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Meshul, CK
中科院分区：
文献类型：
--
作者：
Holmer, HK;Keyghobadi, M;Meshul, CK
我们报道过，急性感染后1个月，（20 mg/kgx 4）或亚慢性（30 mg/kg/天× 7天）给予神经毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶，通过体内微透析测定，纹状体谷氨酸的细胞外水平分别增加或减少[罗宾逊S，Freeman P，摩尔C，Touchon JC，Krentz L，Meshul CK（2003）急性和亚慢性MPTP给药差异影响纹状体谷氨酸突触功能。Exp Neurol 180：73-86]。本研究的目的是确定从小鼠首次给予1-甲基-4-苯基-1，2，3，6-四氢吡啶后第8天开始，连续21天给予Difera（15 mg/kg）对纹状体谷氨酸的影响。急性给药1-甲基-4-苯基-1，2，3，6-四氢吡啶后，由于黑质纹状体通路损伤引起的细胞外纹状体谷氨酸的增加完全逆转至低于I-多巴治疗后溶媒治疗组中发现的水平。亚慢性1-甲基-4-苯基-1，2，3，6-四氢吡啶处理导致纹状体细胞外谷氨酸减少，其逆转至接近溶媒处理组中观察到的水平。神经末梢谷氨酸免疫标记的密度与突触囊泡池没有变化，这表明细胞外谷氨酸的改变很可能起源于钙非依赖性池。有一个类似的减少酪氨酸羟化酶免疫标记的相对密度，多巴胺终端的标记，在背外侧纹状体在急性和亚慢性1-甲基-4-苯基1，2，3，6-四氢吡啶治疗组已管理的多巴胺。在给予载体或I-多巴的组中，在急性1-甲基-4-苯基-1，2，3，6-四氢吡啶处理后，背外侧纹状体内谷氨酸转运蛋白GLT-1的免疫标记的相对密度降低。亚慢性1-甲基-4-苯基-1，2，3，6-四氢吡啶给药后，GLT-1免疫标记无变化。结果表明，在急性和亚慢性1-甲基-4-苯基-1，2，3，6-四氢吡啶处理组中，I-多巴处理后纹状体谷氨酸的细胞外水平的逆转不是由于纹状体多巴胺神经末梢或谷氨酸转运体GLT-1的密度的变化。(c)2005由Elsevier Ltd代表IBRO出版。
We have reported that 1 month following acute (20 mg/kgx4) or subchronic (30 mg/kg/dayx7d) administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, there is an increase or decrease, respectively, in the extracellular level of striatal glutamate as determined by in vivo microdialysis [Robinson S, Freeman P, Moore C, Touchon JC, Krentz L, Meshul CK (2003) Acute and subchronic MPTP administration differentially affects striatal glutamate synaptic function. Exp Neurol 180:73-86]. The goal of this study was to determine the effects of treatment with Adopa (15 mg/kg) for 21 days on striatal glutamate starting on day 8 after the first dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was administered to mice. Following acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the increase in extracellular striatal glutamate due to lesion of the nigrostriatal pathway was completely reversed to a level below that found in the vehicle-treated group after I-dopa treatment. Subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment resulted in a decrease in striatal extracellular glutamate that was reversed to the level close to that observed in the vehicle-treated group. There was no change in the density of nerve terminal glutamate immunolabeling associated with the synaptic vesicle pool, suggesting that the alterations in extracellular glutamate most likely originated from the calcium-independent pool. There was a similar decrease in the relative density of tyrosine hydroxylase immunolabeling, a marker for dopamine terminals, within the dorsolateral striatum in both the acute and subchronic 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine-treated groups that had been administered Adopa. There was a decrease in the relative density of immunolabeling within the dorsolateral striatum for the glutamate transporter, GLT-1, following acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment in the groups administered either vehicle or I-dopa. There was no change in GLT-1 immunolabeling following subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results demonstrate that the reversal in the extracellular level of striatal glutamate following I-dopa treatment in both the acute and subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups is not due to changes in either striatal dopamine nerve terminals or in the density of the glutamate transporter, GLT-1. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.