A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats.
A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats.
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DOI：
10.1002/brb3.11
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发表时间：
2011-09
影响因子：
3.1
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
--
作者：
Choudhury, Mohammed Emamussalehin;Sugimoto, Kana;Kubo, Madoka;Nagai, Masahiro;Nomoto, Masahiro;Takahashi, Hisaaki;Yano, Hajime;Tanaka, Junya
多巴胺（DA）激动剂被广泛用作帕金森病的主要治疗。然而，它们不能阻止多巴胺能神经元的进行性变性，这是该疾病的中心病理学。在这项研究中，我们发现，皮下注射含有粒细胞巨噬细胞集落刺激因子和白细胞介素-3（IL-3）的细胞因子混合物显着抑制多巴胺能神经变性6-羟基多巴胺损伤的大鼠，帕金森氏病的动物模型。细胞因子混合物抑制纹状体DA含量的下降，改善损伤大鼠的运动功能。在响应细胞因子注射，多巴胺能神经元在黑质pars延髓增加抗凋亡蛋白Bcl-xL的表达。在注射生理盐水和奎宁的大鼠中，丘脑部的小胶质细胞活化是明显的。然而，细胞因子混合物抑制促炎细胞因子IL-1β和肿瘤坏死因子α的表达，并上调神经保护因子胰岛素样生长因子1和肝细胞生长因子。在培养的小胶质细胞中观察到类似的反应。详细的形态学分析显示，NG 2蛋白聚糖表达的神经胶质细胞增加，在注射精氨酸的大鼠，而星形胶质细胞活化与抗氧化因子的表达增加是显而易见的，只有在盐水注射的大鼠。因此，本研究结果表明，细胞因子混合物在抑制神经变性方面是显著有效的。其神经保护作用可能是通过增加多巴胺能神经元中Bcl-xL的表达以及激活促进神经元存活的小胶质细胞的有益作用来介导的。此外，这种细胞因子混合物可能对NG 2蛋白聚糖表达神经胶质细胞有间接作用，其作用可能与神经元存活有关。
Dopamine (DA) agonists are widely used as primary treatments for Parkinson's disease. However, they do not prevent progressive degeneration of dopaminergic neurons, the central pathology of the disease. In this study, we found that subcutaneous injection of a cytokine mixture containing granulocyte macrophage colony-stimulating factor and interleukin-3 (IL-3) markedly suppressed dopaminergic neurodegeneration in 6-hydroxydopamine-lesioned rats, an animal model of Parkinson's disease. The cytokine mixture suppressed the decrease of DA content in the striatum, and ameliorated motor function in the lesioned rats. In response to the cytokine injection, dopaminergic neurons in the substantia nigra pars compacta increased expression of the antiapoptotic protein Bcl-xL. Microglial activation in the pars compacta was evident in both the saline- and cytokine-injected rats. However, the cytokine mixture suppressed expression of the proinflammatory cytokines IL-1β and tumor necrosis factors α, and upregulated the neuroprotective factors insulin-like growth factor-1 and hepatocyte growth factor. Similar responses were observed in cultured microglia. Detailed morphometric analyses revealed that NG2 proteoglycan-expressing glial cells increased in the cytokine-injected rats, while astrocytic activation with increased expression of antioxidative factors was evident only in the saline-injected rats. Thus, the present findings show that the cytokine mixture was markedly effective in suppressing neurodegeneration. Its neuroprotective effects may be mediated by increased expression of Bcl-xL in dopaminergic neurons, and the activation of beneficial actions of microglia that promote neuronal survival. Furthermore, this cytokine mixture may have indirect actions on NG2 proteoglycan-expressing glia, whose role may be implicated in neuronal survival.
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影响因子：
5.1
作者：
Lue, Lih-Fen;Kuo, Yu-Min;Beach, Thomas;Walker, Douglas G.
通讯作者：
Walker, Douglas G.
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
影响因子：
2.9
作者：
Ohya, Wakana;Funakoshi, Hiroshi;Nakamura, Toshikazu
通讯作者：
Nakamura, Toshikazu
影响因子：
--
作者：
Cullheim, Staffan;Thams, Sebastian
通讯作者：
Thams, Sebastian
影响因子：
5.3
作者：
Clarkson, ED;Zawada, WM;Freed, CR
通讯作者：
Freed, CR