Histological Correlates of Neuroanatomical Changes in a Rat Model of Levodopa-Induced Dyskinesia Based on Voxel-Based Morphometry.
Histological Correlates of Neuroanatomical Changes in a Rat Model of Levodopa-Induced Dyskinesia Based on Voxel-Based Morphometry.
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基于体素形态测量的左旋多巴诱发的运动障碍大鼠模型神经解剖学变化的组织学相关性
DOI：
10.3389/fnagi.2021.759934
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发表时间：
2021
影响因子：
4.8
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Zhang X;Chen W;Wu Y;Zeng W;Yuan Y;Cheng C;Yang X;Wang J;Yang X;Xu Y;Lei H;Cao X;Xu Y
长期使用左旋多巴治疗帕金森病(PD)患者经常会引发运动并发症，称为L多巴诱发的运动障碍(LID)。然而，从神经解剖学的角度探讨LID的发病机制的研究很少。本研究旨在研究LID大鼠模型的宏观结构变化及其潜在的组织学机制。首先，通过立体定向向右侧前脑束内侧注射6-羟基多巴胺(6-OHDA)建立偏侧帕金森病大鼠模型，然后给予生理盐水(PD)或L多巴诱发LID。在不同时间点进行磁共振成像(MRI)和行为学评估。组织学分析以评估MRI信号变化与细胞因素之间的相关性。基于体素的形态计量学(VBM)分析显示，与假手术组相比，帕金森病大鼠双侧皮质和皮质下区域的体积逐渐减少。长期给予L多巴可部分逆转上述改变，且损毁侧纹状体背外侧区、黑质和梨状皮质体积较帕金森病组显著增加。在纹状体细胞水平上，PD大鼠损伤侧背外侧纹状体胶质纤维酸性蛋白阳性(GFAP+)星形胶质细胞明显多于健侧和假手术组。延长L-多巴治疗时间进一步增加胶质纤维酸性蛋白水平。6-羟基多巴胺损伤和L-多巴处理均不影响纹状体血管内皮生长因子的表达。此外，与PD大鼠相比，LID大鼠损毁的纹状体中突触相关蛋白(SYP、PSD95和SAP97)有相当大的增加。高尔基-考克斯染色树突棘形态分析显示，慢性L-多巴治疗后树突棘密度增加。综上所述，我们的发现提示LID大鼠纹状体体积的变化涉及同侧纹状体星形胶质细胞的激活、突触超微结构和信号蛋白的丰富。同时，这些数据突显了结构性MRI，特别是VBM分析在确定LID啮齿动物模型的形态表型方面的巨大潜力。
Long-term therapy with levodopa (L-DOPA) in patients with Parkinson’s disease (PD) often triggers motor complications termed as L-DOPA-induced dyskinesia (LID). However, few studies have explored the pathogenesis of LID from the perspective of neuroanatomy. This study aimed to investigate macroscopic structural changes in a rat model of LID and the underlying histological mechanisms. First, we established the hemiparkinsonism rat model through stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, followed by administration of saline (PD) or L-DOPA to induce LID. Magnetic resonance imaging (MRI) and behavioral evaluations were performed at different time points. Histological analysis was conducted to assess the correlations between MRI signal changes and cellular contributors. Voxel-based morphometry (VBM) analysis revealed progressive bilateral volume reduction in the cortical and subcortical areas in PD rats compared with the sham rats. These changes were partially reversed by chronic L-DOPA administration; moreover, there was a significant volume increase mainly in the dorsolateral striatum, substantia nigra, and piriform cortex of the lesioned side compared with that of PD rats. At the striatal cellular level, glial fibrillary acidic protein-positive (GFAP+) astrocytes were significantly increased in the lesioned dorsolateral striatum of PD rats compared with the intact side and the sham group. Prolonged L-DOPA treatment further increased GFAP levels. Neither 6-OHDA damage nor L-DOPA treatment influenced the striatal expression of vascular endothelial growth factor (VEGF). Additionally, there was a considerable increase in synapse-associated proteins (SYP, PSD95, and SAP97) in the lesioned striatum of LID rats relative to the PD rats. Golgi-Cox staining analysis of the dendritic spine morphology revealed an increased density of dendritic spines after chronic L-DOPA treatment. Taken together, our findings suggest that striatal volume changes in LID rats involve astrocyte activation, enrichment of synaptic ultrastructure and signaling proteins in the ipsilateral striatum. Meanwhile, the data highlight the enormous potential of structural MRI, especially VBM analysis, in determining the morphological phenotype of rodent models of LID.
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影响因子：
4.7
作者：
Dupre KB;Eskow KL;Barnum CJ;Bishop C
通讯作者：
Bishop C
影响因子：
4.3
作者：
Chen G;Nie S;Han C;Ma K;Xu Y;Zhang Z;Papa SM;Cao X
通讯作者：
Cao X
影响因子：
8.6
作者：
Bezard, Erwan;Tronci, Elisabetta;Carta, Manolo
通讯作者：
Carta, Manolo
影响因子：
4.1
作者：
Cerasa, Antonio;Salsone, Maria;Quattrone, Aldo
通讯作者：
Quattrone, Aldo
影响因子：
3.4
作者：
Aljuaid, Maram;Booth, Samuel;Ko, Ji Hyun
通讯作者：
Ko, Ji Hyun