FGF18 PROTECTS AGAINST 6-HYDROXYDOPAMINE-INDUCED NIGROSTRIATAL DAMAGE IN A RAT MODEL OF PARKINSON'S DISEASE
FGF18 PROTECTS AGAINST 6-HYDROXYDOPAMINE-INDUCED NIGROSTRIATAL DAMAGE IN A RAT MODEL OF PARKINSON'S DISEASE
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DOI：
10.1016/j.neuroscience.2017.05.007
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发表时间：
2017-07-25
期刊：
影响因子：
3.3
通讯作者：
Liu, Jianmin
中科院分区：
文献类型：
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作者：
Guo, Xingzhi;Liu, Tingting;Liu, Jianmin
黑质多巴胺能神经元损伤是帕金森病(PD)的病理特征。然而，这种损伤的潜在机制仍然难以捉摸。由于成纤维细胞生长因子18(FGF18)参与了中脑发育，并被报道对神经元的缺血损伤具有保护作用，我们研究了FGF18是否对黑质中的多巴胺能神经元起到保护作用。体外实验数据显示，FGF18通过AKT/GSK3β信号通路显著改善6-羟基多巴胺(6-OHDA)的神经毒性。对6-OHDA诱导的帕金森病大鼠模型的进一步研究表明，FGF18改善了帕金森病大鼠的行为障碍，并减少了黑质酪氨酸羟化酶(TH)阳性神经元的丢失。此外，6-OHDA可引起TH阳性纤维的丢失，而FGF18可逆转这一作用。综上所述，这些数据表明，FGF18在6-OHDA诱导的PD大鼠模型中对黑质纹状体系统的帕金森样神经变性具有保护作用，基于FGF18的进一步药物发现对PD治疗具有潜在的作用。(C)2017年IBRO。爱思唯尔有限公司出版。保留所有权利。
Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD). However, the underlying mechanism of this injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in midbrain development and has been reported to protect neurons from ischemic injury, we investigated whether FGF18 exerted a protective effect on dopaminergic neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3 beta signaling pathway. Further study of the 6-OHDA-induced PD rat model indicated that FGF18 improved the behavioral dysfunction in PD rats and reduced the tyrosine hydroxylase (TH)-positive neuronal loss in the SN. In addition, 6-OHDA induced a loss of TH-positive fibers that was reversed by pretreatment with FGF18. Taken together, these data suggest that FGF18 plays a protective role against parkinsonian neurodegeneration in the nigrostriatal system in a 6-OHDA-induced PD rat model and that further drug discovery based on FGF18 has a potential role for PD therapy. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.