Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro.
Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro.
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DOI：
10.1186/s12974-016-0480-3
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发表时间：
2016-01-26
影响因子：
9.3
通讯作者：
Finch CE
中科院分区：
文献类型：
--
作者：
Cheng H;Davis DA;Hasheminassab S;Sioutas C;Morgan TE;Finch CE
空气污染与人类神经退行性变化的基础正在啮齿动物模型中进行研究。我们和其他人发现，来自汽车尾气的超细颗粒物（PM）可以在体内和体外诱导突触功能障碍和炎症反应。特别是，来自当地城市交通走廊的颗粒物质（nPM, PM0.2）的纳米级亚组分可以诱导来自新生大鼠大脑皮层的混合胶质细胞（星形胶质细胞和小胶质细胞）的胶质细胞TNFα的产生。在这里，我们研究了TNFα在12 μg/ml的水悬浮液中nPM诱导的神经突功能障碍中的作用。首先，我们发现nPM的近端脑通道嗅觉神经上皮（OE）在体外对nPM快速反应，诱导TNFα，激活巨噬细胞和树突收缩。用新生大鼠大脑皮层混合胶质细胞和神经元进一步分析细胞相互作用。小胶质细胞对nPM诱导TNFα的作用大于星形胶质细胞。然后，我们发现混合胶质细胞条件培养基（nPM-CM）中三倍高的TNFα是通过小干扰RNA (siRNA) TNFα敲低和TNFα免疫中和抑制神经突生长的原因。尽管nPM在OE中缺乏TNFR1诱导，但TNFα受体阻滞剂阻断TNFR1的实验恢复了总神经突长度。这些发现暗示小胶质细胞来源的TNFα在空气污染相关的神经退行性改变中作为nPM的介质，改变突触功能和神经元生长。
The basis for air pollution-associated neurodegenerative changes in humans is being studied in rodent models. We and others find that the ultrafine particulate matter (PM) derived from vehicular exhaust can induce synaptic dysfunction and inflammatory responses in vivo and in vitro. In particular, a nano-sized subfraction of particulate matter (nPM, PM0.2) from a local urban traffic corridor can induce glial TNFα production in mixed glia (astrocytes and microglia) derived from neonatal rat cerebral cortex. Here, we examine the role of TNFα in neurite dysfunctions induced by nPM in aqueous suspensions at 12 μg/ml. First, we show that the proximal brain gateway to nPM, the olfactory neuroepithelium (OE), rapidly responds to nPM ex vivo, with induction of TNFα, activation of macrophages, and dendritic shrinkage. Cell interactions were further analyzed with mixed glia and neurons from neonatal rat cerebral cortex. Microglia contributed more than astrocytes to TNFα induction by nPM. We then showed that the threefold higher TNFα in conditioned media (nPM-CM) from mixed glia was responsible for the inhibition of neurite outgrowth by small interfering RNA (siRNA) TNFα knockdown and by TNFα immunoneutralization. Despite lack of TNFR1 induction by nPM in the OE, experimental blocking of TNFR1 by TNFα receptor blockers restored total neurite length. These findings implicate microglia-derived TNFα as a mediator of nPM in air pollution-associated neurodegenerative changes which alter synaptic functions and neuronal growth.