Loss of Collapsin Response Mediator Protein 4 Attenuates 6-Hydroxydopamine-Induced Impairments in a Mouse Model of Parkinson’s Disease
Loss of Collapsin Response Mediator Protein 4 Attenuates 6-Hydroxydopamine-Induced Impairments in a Mouse Model of Parkinson’s Disease
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帕金森病小鼠模型中崩溃蛋白反应介导蛋白 4 的缺失可减轻 6-羟基多巴胺诱导的损伤
DOI：
10.1007/s11064-020-03086-z
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发表时间：
2020
影响因子：
4.4
通讯作者：
Ohshima Toshio
中科院分区：
文献类型：
--
作者：
Li Wenting;Goshima Yoshio;Ohshima Toshio
帕金森病（Parkinson's disease，PD）是一种慢性神经退行性疾病，其特征是由黑质多巴胺能神经元变性引起的运动功能障碍。许多因素被推测在PD的机制中起作用，包括氧化应激、线粒体功能障碍、蛋白质处理异常以及PD诱导的细胞凋亡。此外，研究人员最近表明，炎症分泌物可能会与星形胶质细胞等邻近细胞接触，然后诱导自分泌和旁分泌反应，放大炎症，导致神经退行性变。在本研究中，我们分析了6-羟基多巴胺（6-OHDA）注射的雄性小鼠中的神经保护和抗炎作用，以及其对运动障碍的影响。我们的研究结果表明，CRMP 4的缺失可以维持纹状体中的TH阳性纤维和SNc中的TH阳性细胞，减轻炎症反应，改善运动协调和旋转行为。此外，基于我们在早期时间点的发现，我们假设Crmp 4 +/+和Crmp 4 −/−小鼠之间的主要差异可能发生在小胶质细胞而不是神经元中。尽管CRMP 4在PD发病机制中的具体作用还有待进一步研究，但我们的研究结果表明，CRMP 4可能成为PD治疗的一个可能靶点。
Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by impaired motor symptoms induced by the degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc). Many factors are speculated to operate in the mechanism of PD, including oxidative stress, mitochondrial dysfunction, abnormal protein handling, and PD induced apoptosis. Besides, researchers have recently shown that inflammatory secretions may engage neighboring cells such as astrocytes, which then induce autocrine and paracrine responses that amplify the inflammation, leading to neurodegeneration. In the present study, we analyzed the neuroprotective and anti-inflammatory effects of collapsin response mediator protein 4 (CRMP4) deletion in 6-hydroxydopamine (6-OHDA)-injected male mice, as well as its effects on motor impairments. Our findings indicated that the deletion of CRMP4 could maintain the TH-positive fibers in the striatum and the TH-positive cells in SNc, attenuate the inflammatory responses, and improve motor coordination and rotational behavior. Furthermore, based on our findings at the early time points, we hypothesized that primary differences between theCrmp4+/+ andCrmp4−/− mice may occur in microglia instead of neurons. Although further work should be carried out to clarify the specific role of CRMP4 in the pathogenesis of PD, our findings suggest that it could be a possible target for the treatment of PD.
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影响因子：
3.4
作者：
Kirik, D;Rosenblad, C;Björklund, A
通讯作者：
Björklund, A
影响因子：
4.8
作者：
Franken, S;Junghans, U;Kappler, J
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影响因子：
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影响因子：
4.2
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影响因子：
5.3
作者：
Bensadoun, JC;Déglon, N;Aebischer, P
通讯作者：
Aebischer, P