Effect of MPTP-induced denervation on basal ganglia GABAB receptors:: Correlation with dopamine concentrations and dopamine transporter
Effect of MPTP-induced denervation on basal ganglia GABAB receptors:: Correlation with dopamine concentrations and dopamine transporter
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DOI：
10.1002/syn.1045
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发表时间：
2001-06-01
期刊：
影响因子：
2.3
通讯作者：
Di Paolo, T
中科院分区：
文献类型：
--
作者：
Calon, F;Lavertu, N;Di Paolo, T
采用受体放射自显影技术和原位杂交技术，研究了mptp诱导的黑质致密部（SNpc）多巴胺能神经元损伤对小鼠和猴子基底神经节GABA(B)受体的影响。通过纹状体儿茶酚胺含量、纹状体I-125-RTI-121与多巴胺转运体（DAT）的结合以及SNpc中DAT的表达来测量损伤程度。利用H-3-CGP54626检测小鼠脑内GABA(B)受体的表达，并利用靶向GABA（B(1a)）、GABA（B(1a)）、GABA（B(1b)）、GABA（B(2)）亚基mrna的寡核苷酸探针检测GABA(B)亚基mrna的表达。在猴子中，使用I-125-CGP64213和GABA（B(1a + B)）和GABA(B(2)) mrna的选择性探针。在小鼠中，MPTP剂量为40 mg/kg后，多巴胺含量、I-125-RTI-121结合和DAT表达分别降低44%、40%和39%，MPTP剂量为120 mg/kg后，分别降低74%、70%和34%。在猴子中，多巴胺含量和DAT表达分别下降了90%和80%以上。在纹状体和丘底核中，GABA(B)受体在MPTP后没有变化。在小鼠SNpc中，MPTP （120 mg/kg）诱导H-3-CGP54626结合显著降低（-10%），GABA(B(1a + B)) mRNA表达显著降低（-13%）。GABA(B(1a + B)) mRNA表达的降低与多巴胺含量、I-125-RTI-121结合和DAT表达相关。在mptp处理的猴子中，I-125-CGP64213结合（-40%），GABA(B(1a + B)) mRNA（-69%）和GABA(B(2)) mRNA（-66%）在SNpc中也显著降低。我们的研究结果表明，mptp诱导的去神经支配与局限于SNpc的GABA(B)受体的减少有关。这些观察结果可能与涉及基底神经节功能障碍的运动障碍（如帕金森病）的病理生理学有关。[j], 2001。(C) 2001 Wiley-Liss, Inc。
We investigated the effect of MPTP-induced lesion of the substantia nigra pars compacta (SNpc) dopaminergic neurons on GABA(B) receptors in the basal ganglia of mice and monkeys using receptor autoradiography and in situ hybridization. The extent of the lesion was measured with striatal catecholamine content, striatal binding of I-125-RTI-121 to dopamine transporter (DAT), and DAT expression in the SNpc. GABA(B) receptors in mice brain were evaluated using H-3-CGP54626 and its expression was measured with oligonucleotides probes targeting the mRNAs of GABA(B(1a + b)), GABA(B(1a)), GABA(B(1b)), GABA(B(2)) subunits. In monkeys, I-125-CGP64213 and selective probes for GABA(B(1a + b)) and GABA(B(2)) mRNAs were used. In mice, dopamine content, I-125-RTI-121 binding, and DAT expression were reduced by 44%, 40%, and 39% after a dose of 40 mg/kg of MPTP and 74%, 70%, and 34% after 120 mg/kg of MPTP, respectively. In monkeys, dopamine content and DAT expression were decreased by more than 90% and 80%, respectively. In the striatum and the subthalamic nucleus, GABA(B) receptors were unchanged following MPTP in both species. In the SNpc of mice, MPTP (120 mg/kg) induced a significant decrease of H-3-CGP54626 binding (-10%) and of the expression of GABA(B(1a + b)) mRNA (-13%). The decrease of the expression of GABA(B(1a + b)) mRNA was correlated with dopamine content, I-125-RTI-121 binding and DAT expression. In MPTP-treated monkeys, I-125-CGP64213 binding (-40%), GABA(B(1a + b)) mRNA (-69%) and GABA(B(2)), mRNA (-66%) were also significantly decreased in the SNpc. Our results suggest that MPTP-induced denervation is associated with a decrease of GABA(B) receptors restricted to the SNpc. These observations may be relevant to the pathophysiology of motor disorders involving dysfunction of the basal ganglia such as Parkinson disease. Synapse 40:225-234, 2001. (C) 2001 Wiley-Liss, Inc.