Laboratório de Neuroquímica e Biologia Celular, Departamento de Bioquímica e Biofísica, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Laboratório de Neuroquímica e Biologia Celular, Departamento de Bioquímica e Biofísica, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Neurotoxicology. 2018 May;66:98-106. doi: 10.1016/j.neuro.2018.03.009. Epub 2018 Mar 26.
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-α and IL-1β production and microglial activation in organotypic midbrain slice cultures from P8 - P9 Wistar rats. We demonstrated aminochrome (25 μM, 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-α, IL-1β mRNA and protein levels. Moreover, aminochrome (25 μM, 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.
最近的证据表明，氨基苯甲酮可诱导与神经炎症相关的神经胶质细胞激活。这种多巴胺衍生的分子诱导α-突触核蛋白寡聚物的形成和稳定、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、内质网应激以及微管网络的破坏，但到目前为止，还没有证据表明它会影响细胞因子和神经营养因子的产生，而这些机制参与了帕金森病 (PD) 中的神经元丧失。本研究探讨了氨基苯甲酮对调节 NGF、GDNF、TNF-α 和 IL-1β 产生以及 P8-P9 期 Wistar 大鼠器官型中脑切片培养物中小胶质细胞激活的潜在作用。我们证明了氨基苯甲酮（25μM，24 小时）可诱导 GFAP 表达减少、NGF 和 GDNF mRNA 水平降低、Iba1 细胞形态改变，以及 TNF-α、IL-1β mRNA 和蛋白水平升高。此外，氨基苯甲酮（25μM，48 小时）可诱导切片边缘的形态变化和 TH 表达减少。这些结果表明神经炎症以及神经营养因子（GDNF 和 NGF）的负调节可能参与了氨基苯甲酮诱导的神经退行性变，并有助于更好地理解 PD 的发病机制。
