Quantitative analyses of GFRalpha-1 and GFRalpha-2 mRNAs and tyrosine hydroxylase protein in the nigrostriatal system reveal bilateral compensatory changes following unilateral 6-OHDA lesions in the rat.
Quantitative analyses of GFRalpha-1 and GFRalpha-2 mRNAs and tyrosine hydroxylase protein in the nigrostriatal system reveal bilateral compensatory changes following unilateral 6-OHDA lesions in the rat.
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对黑质纹状体系统中 GFRα-1 和 GFRα-2 mRNA 以及酪氨酸羟化酶蛋白的定量分析揭示了大鼠单侧 6-OHDA 损伤后的双侧代偿性变化。
DOI：
10.1016/j.brainres.2004.05.003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Bohn,MC
中科院分区：
文献类型：
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作者：
Kozlowski,DA;Miljan,EA;Bremer,EG;Harrod,CG;Gerin,C;Connor,B;George,D;Larson,B;Bohn,MC
通过实时定量 RT-PCR (QRT-PCR) 测定 GFRα-1 和 GFRα-2（胶质细胞系源性神经营养因子 (GDNF) 和神经营养因子 (NTN) 的首选受体）的 mRNA 拷贝数。分别评估正常大鼠的纹状体（ST）和黑质（SN）以及注射到内侧前脑束或 ST 的 6-OHDA 急性或进行性损伤的大鼠的受体表达。在正常 ST 中可以清楚地检测到 GFRα-1 mRNA。在正常 SN 中，观察到两种受体的表达显着升高。急性病变后4周，双侧SN中GFRα-2 mRNA显着减少，而SN和ST中GFRα-1 mRNA不受影响。进行性病变导致双侧 ST 中 GFRα1 mRNA 逐渐减少。在 SN 中，GFRα-1 mRNA 水平并未受到进展性病变的显着影响，而 GFRα-2 mRNA 双侧显着降低。针对 PC12 细胞酪氨酸羟化酶 (TH) 蛋白进行标准化的定量蛋白质印迹显示，在急性和进行性病变后 4 周，病变 SN 中的 TH 蛋白出现预期下降，但对侧未病变 SN 中的 TH 蛋白也显着增加。这些数据表明，黑质纹状体系统中先前未被认识到的代偿性变化是由于单侧多巴胺耗竭而发生的。由于观察到的受体表达变化并不总是与多巴胺神经元的损失同时发生，因此除了黑质多巴胺神经元之外的细胞似乎也受到 6-OHDA 损伤的影响，并且是神经营养因子 GDNF 和 NTN 的潜在靶标。
Copy numbers of mRNAs for GFRα-1 and GFRα-2, the preferred receptors for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) were determined by real-time quantitative RT-PCR (QRT-PCR). Receptor expression was assessed in striatum (ST) and substantia nigra (SN) of normal rats and rats acutely or progressively lesioned by 6-OHDA injected into the medial forebrain bundle or ST, respectively. GFRα-1 mRNA was clearly detected in normal ST. In normal SN, significantly higher expression of both receptors was observed. At 4 weeks after acute lesion, GFRα-2 mRNA was markedly decreased in SN bilaterally, whereas GFRα-1 mRNA in SN and ST was not affected. A progressive lesion resulted in a progressive decrease of GFRα1 mRNA in ST bilaterally. In SN, levels of GFRα-1 mRNA were not significantly affected by a progressive lesion, whereas GFRα-2 mRNA was markedly decreased bilaterally. Quantitative western blotting standardized against tyrosine hydroxylase (TH) protein from PC12 cells revealed the expected decrease in TH protein in lesioned SN, but also significant increases in TH protein in contralateral, unlesioned SNs at 4 weeks after both acute and progressive lesions. These data suggest that previously unrecognized compensatory changes in the nigrostriatal system occur in response to unilateral dopamine depletion. Since the changes observed in receptor expression did not always parallel loss of dopamine neurons, cells in addition to the nigral dopamine neurons appear to be affected by a 6-OHDA insult and are potential targets for the neurotrophic factors, GDNF and NTN.