Aminochrome decreases NGF, GDNF and induces neuroinflammation in organotypic midbrain slice cultures
Aminochrome decreases NGF, GDNF and induces neuroinflammation in organotypic midbrain slice cultures
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DOI：
10.1016/j.neuro.2018.03.009
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发表时间：
2018-05-01
期刊：
影响因子：
3.4
通讯作者：
Silva, Victor Diogenes A.
中科院分区：
文献类型：
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作者：
de Araujo, Fillipe M.;Ferreir, Rafael S.;Silva, Victor Diogenes A.
最近的证据表明，氨基色素可诱导与神经炎症相关的神经胶质活化。这种多巴胺衍生的分子诱导α -突触核蛋白低聚物的形成和稳定、线粒体功能障碍、氧化应激、蛋白酶体和溶酶体系统功能障碍、内质网应激和微管网络破坏，但到目前为止，还没有证据表明它对细胞因子和神经营养因子的产生有影响，而这些是帕金森病（PD）中神经元丢失的机制。本研究探讨了氨基色素在P8 - P9 Wistar大鼠器官型中脑切片培养中调节NGF、GDNF、tnf - α和IL-1 β的产生和小胶质细胞激活中的潜在作用。我们证明了氨基色素（25 μ M, 24 h）诱导GFAP表达降低，NGF和GDNF mRNA水平降低，Iba1（+）细胞形态学改变，tnf - α， IL-1 β mRNA和蛋白水平升高。此外，氨基色素（25 μ M）作用48 h可引起切片边缘形态变化和TH表达降低。这些结果表明，神经炎症以及神经营养因子（GDNF和NGF）的负调控可能参与了氨基色素诱导的神经变性，并有助于更好地了解PD的发病机制。(C) 2018 Elsevier B.V.版权所有
Recent evidence shows that aminochrome induces glial activation related to neuroinflammation. This dopamine derived molecule induces formation and stabilization of alpha-synuclein oligomers, mitochondria dysfunction, oxidative stress, dysfunction of proteasomal and lysosomal systems, endoplasmic reticulum stress and disruption of the microtubule network, but until now there has been no evidence of effects on production of cytokines and neurotrophic factors, that are mechanisms involved in neuronal loss in Parkinson's disease (PD). This study examines the potential role of aminochrome on the regulation of NGF, GDNF, TNF-alpha and IL-1 beta production and microglial activation in organotypic midbrain slice cultures from P8 - P9 Wistar rats. We demonstrated aminochrome (25 mu M, for 24 h) induced reduction of GFAP expression, reduction of NGF and GDNF mRNA levels, morphological changes in Iba1(+) cells, and increase of both TNF-alpha, IL-1 beta mRNA and protein levels. Moreover, aminochrome (25 mu M, for 48 h) induced morphological changes in the edge of slices and reduction of TH expression. These results demonstrate neuroinflammation, as well as negative regulation of neurotrophic factors (GDNF and NGF), may be involved in aminochrome-induced neurodegeneration, and they contribute to a better understanding of PD pathogenesis. (C) 2018 Elsevier B.V. All rights reserved.