The effect of 6-hydroxydopamine lesions on the release of amino acids in the direct and indirect pathways of the basal ganglia: a dual microdialysis probe analysis
The effect of 6-hydroxydopamine lesions on the release of amino acids in the direct and indirect pathways of the basal ganglia: a dual microdialysis probe analysis
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DOI：
10.1046/j.1460-9568.2003.02795.x
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发表时间：
2003-08-01
影响因子：
3.4
通讯作者：
Della Corte, L
中科院分区：
文献类型：
--
作者：
Bianchi, L;Galeffi, F;Della Corte, L
帕金森病和帕金森病动物模型中黑质多巴胺能神经元的丧失与通过基底神经节的信息流的所谓“直接”和“间接”途径的活动不平衡有关。本研究的目的是通过双探针微透析，确定这种不平衡是否反映在通路中GABA、天冬氨酸和谷氨酸的释放变化上。在新纹状体、黑质或苍白球植入微透析探针，分析透析液中氨基酸的释放情况。基础氨基酸水平基本未受6-OHDA损伤的影响；然而，受损大鼠苍白球透析液中的GABA水平显著升高，表明间接途径的不平衡。在新纹状体中使用kainic酸可以增强GABA在局部和远端黑质和苍白球的释放。在6- ohda损伤大鼠中，刺激释放的GABA在黑质中被消除，表明沿直接途径的传播减少。因此，与基底节区直接-间接通路模型一致，6-OHDA损伤导致纹状体（间接）通路中GABA的基底释放升高，纹状体（直接）通路中诱发的GABA释放减少。这些不平衡可能是帕金森氏症和帕金森氏症动物模型中运动异常的基础，至少是部分原因。
The loss of dopaminergic neurons of the substantia nigra in Parkinson's disease and in animal models of Parkinson's disease is associated with an imbalance in the activity of the so-called 'direct' and 'indirect' pathways of information flow through the basal ganglia. The aim of the present study was to determine whether the imbalance is reflected in changes in the release of GABA, aspartate and glutamate in the pathways using dual probe microdialysis in freely moving rats. Control and 6-hydroxydopamine-(6-OHDA)-lesioned rats were implanted with microdialysis probes in the neostriatum and substantia nigra or globus pallidus and the release of amino acids was analysed in the dialysates. Basal levels of amino acids were largely unaltered by the 6-OHDA lesion; however, the levels of GABA in the globus pallidus dialysates were significantly elevated in the lesioned rats, indicating an imbalance in favour of the indirect pathway. Administration of kainic acid to the neostriatum enhanced the release of GABA locally and in the distal probes in the substantia nigra and globus pallidus. In 6-OHDA-lesioned rats, stimulated release of GABA in the substantia nigra was abolished, indicating a reduction in transmission along the direct pathway. Thus, consistent with the direct-indirect pathway model of the basal ganglia, the 6-OHDA lesion results in an elevation of the basal release of GABA in the striatopallidal (indirect) pathway and a reduction in the evoked release of GABA in the striatonigral (direct) pathway. These imbalances may underlie, at least in part, the motor abnormalities of Parkinson's disease and in animal models of Parkinson's disease.