ADAPTIVE GENE EXPRESSION CHANGES ON THE HEALTHY SIDE OF PARKINSONIAN RATS
ADAPTIVE GENE EXPRESSION CHANGES ON THE HEALTHY SIDE OF PARKINSONIAN RATS
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DOI：
10.1016/j.neuroscience.2012.12.027
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发表时间：
2013-03-13
期刊：
影响因子：
3.3
通讯作者：
Kaelin-Lang, A.
中科院分区：
文献类型：
--
作者：
Capper-Loup, C.;Frey, C. M.;Kaelin-Lang, A.
帕金森病(PD)是一种不对称的神经退行性疾病，受影响较小的一侧的二级适应机制可能会补偿帕金森症状。在这里，我们分析了单侧帕金森病大鼠模型健康侧基因表达的变化，并将这些变化与运动速度关联起来，运动速度是已知的帕金森病患者运动速度降低的原因。在单侧6-羟基多巴胺损毁4周后，记录大鼠在脑提取前的自发运动速度。然后，我们用原位杂交组织化学方法分析了直接通路(强啡肽和D1类多巴胺受体)和间接通路(脑啡肽和D2类多巴胺受体)在健侧纹状体的基因表达水平。此外，我们还分析了纹状体和皮质谷氨酸能标记物以及黑质酪氨酸羟化酶(TH)和黑质多巴胺转运体(DAT)的表达。我们发现帕金森病大鼠对侧多巴胺受体基因表达水平与术后4周的平均运动速度呈显著正相关，而对照组则无相关关系。此外，我们观察到与对照组相比，帕金森病大鼠对侧纹状体外侧区强啡肽mRNA的水平显著增加。相反，纹状体间接通路没有观察到对侧的变化。我们也没有发现帕金森病动物对侧TH、DAT或谷氨酸能标志物的显著改变，这表明直接通路基因的变化不是由于黑质纹状体多巴胺能或皮质纹状体谷氨酸能神经支配。总之，我们的结果表明，健康的纹状体直接通路在对抗多巴胺能去神经对运动症状的影响方面发挥了作用。(C)2012年IBRO。爱思唯尔有限公司出版。保留所有权利。
Parkinson's disease (PD) is an asymmetric neurodegenerative disorder, and secondary adaptive mechanisms of the less-affected side could potentially compensate for parkinsonian symptoms. Here, we analyzed gene expression changes on the healthy side of a unilateral PD rat model and correlated these changes with locomotor velocity, which is known to be decreased in PD. Four weeks after a unilateral 6-hydroxydopamine lesion, the spontaneous locomotor velocity of rats was recorded just prior to brain extraction. We then analyzed the gene expression levels of markers of the direct (dynorphin and D1-class dopamine receptors) and indirect (enkephalin and D2-class dopamine receptors) pathways in the contralateral healthy striatum by in situ hybridization histochemistry. In addition, we analyzed the expression of several striatal and cortical glutamatergic markers, as well as nigral tyrosine hydroxylase (TH) and nigral dopamine transporter (DAT). We found a significant positive correlation between the mRNA expression levels of contralateral D1-class dopamine receptors and the mean locomotor velocity, at 4 weeks after surgery in parkinsonian rats but not in controls. Moreover, we observed a significant increase in the level of dynorphin mRNA in the lateral part of the contralateral striatum of parkinsonian rats compared to the controls. In contrast, no contralateral changes were observed in the striatal indirect pathway. We also did not find any significant contralateral modifications of TH, DAT or glutamatergic markers in PD animals, indicating that changes in direct pathway genes are not due to nigrostriatal dopaminergic or corticostriatal glutamatergic innervation. In conclusion, our results suggest a role of the healthy striatal direct pathway in counteracting dopaminergic denervation effects on motor symptoms. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.