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首页> 外文期刊>Cell and Tissue Research >Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice
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Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice

机译：Gdf-15缺乏症不会改变MPTP中毒小鼠黑纹状体多巴胺能系统的脆弱性

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摘要

Growth/differentiation factor-15 (Gdf-15) is a member of the transforming growth factor-beta (Tgf-beta) superfamily and has been shown to be a potent neurotrophic factor for midbrain dopaminergic (DAergic) neurons both in vitro and in vivo. Gdf-15 has also been shown to be involved in inflammatory processes. The aim of this study was to identify the role of endogenous Gdf-15 in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease (PD) by comparing Gdf-15 (+/+) and Gdf-15 (-/-) mice. At 4 days and 14 days post-MPTP administration, both Gdf-15 (+/+) and Gdf-15 (-/-) mice showed a similar decline in DAergic neuron numbers and in striatal dopamine (DA) levels. This was followed by a comparable restorative phase at 90 days and 120 days, indicating that the absence of Gdf-15 does not affect the susceptibility or the recovery capacity of the nigrostriatal system after MPTP administration. The MPTP-induced microglial and astrocytic response was not significantly altered between the two genotypes. However, pro-inflammatory and anti-inflammatory cytokine profiling revealed the differential expression of markers in Gdf-15 (+/+) and Gdf-15 (-/-) mice after MPTP administration. Thus, the MPTP mouse model fails to uncover a major role of endogenous Gdf-15 in the protection of MPTP-lesioned nigrostriatal DAergic neurons, in contrast to its capacity to protect the 6-hydroxydopamine-intoxicated nigrostriatal system.
机译：生长/分化因子15（Gdf-15）是转化生长因子-β（Tgf-beta）超家族的成员，并且在体外和体内均表现出对中脑多巴胺能（DAergic）神经元有效的神经营养因子。 。 Gdf-15也已显示参与炎症过程。这项研究的目的是通过比较Gdf-15来确定内源性Gdf-15在帕金森氏病（PD）的MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）小鼠模型中的作用（+ / +）和Gdf-15（-/-）小鼠。在MPTP给药后4天和14天，Gdf-15（+ / +）和Gdf-15（-/-）小鼠在DAergic神经元数量和纹状体多巴胺（DA）水平上均表现出相似的下降。随后在90天和120天进行了类似的恢复，表明在MPTP给药后，缺乏Gdf-15不会影响黑纹状体系统的敏感性或恢复能力。在两种基因型之间，MPTP诱导的小胶质细胞和星形细胞反应没有显着改变。但是，促炎和抗炎细胞因子谱显示在MPTP给药后，Gdf-15（+ / +）和Gdf-15（-/-）小鼠中标志物的差异表达。因此，与其保护6-羟基多巴胺中毒的黑纹状体系统的能力相反，MPTP小鼠模型未能揭示内源性Gdf-15在保护MPTP损伤的黑纹状体DA能神经元中的主要作用。

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