Changes in neurotransmitter levels and proinflammatory cytokine mRNA expressions in the mice olfactory bulb following nanoparticle exposure
Changes in neurotransmitter levels and proinflammatory cytokine mRNA expressions in the mice olfactory bulb following nanoparticle exposure
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DOI：
10.1016/j.taap.2007.09.009
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发表时间：
2008-01-15
影响因子：
3.8
通讯作者：
Fujimaki, Hidekazu
中科院分区：
文献类型：
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作者：
Tin-Tin-Win-Shwe;Mitsushima, Dai;Fujimaki, Hidekazu
最近，越来越多的报道称，纳米级的颗粒物成分可以到达大脑，可能与神经退行性疾病有关。此前，我们实验室研究了鼻腔滴入纳米炭黑(14 nm和95 nm)对脑细胞因子和趋化因子mRNA表达的影响，发现14 nm炭黑增加了小鼠嗅球中IL-1β、TNF-α、CCL2和CCL3的mRNA表达，而不是在海马区。为了研究单次注射纳米颗粒对小鼠嗅球神经递质和促炎细胞因子的影响，我们进行了活体微透析和实时聚合酶链式反应(Real-time PCR)方法。10周龄雄性BALB/c小鼠右侧嗅球植入导引管，1周后滴入赋形剂或CB(14 nm，250 mg)。注射纳米粒6h后，小鼠腹腔注射生理盐水或细菌细胞壁成分脂磷壁酸(LTA)50mgLTA，可增强CB诱导的神经效应。与对照组相比，CB灌输组小鼠嗅球细胞外谷氨酸和甘氨酸水平显著增加。此外，我们发现LTA进一步增加了谷氨酸和甘氨酸的水平。然而，牛磺酸和GABA水平在同一只小鼠的嗅球中没有观察到变化。我们还检测了赋形剂或CB滴注后11h嗅球的免疫学变化，发现CB和LTA处理的小鼠与对照组相比，IL-1βmRNA的表达显著增加。然而，与对照组相比，CB和生理盐水处理组小鼠的肿瘤坏死因子-αmRNA表达显著增加。这些结果表明，纳米CB可能与LTA协同调节小鼠嗅球细胞外氨基酸类神经递质水平和促炎细胞因子IL-1βmRNA的表达。(C)2007 Elsevier Inc.保留所有权利。
Recently, there have been increasing reports that nano-sized component of particulate matter can reach the brain and may be associated with neurodegenerative diseases. Previously, our laboratory has studied the effect of intranasal instillation of nano-sized carbon black (CB) (14 nm and 95 nm) on brain cytokine and chemokine mRNA expressions and found that 14-nm CB increased IL-1 beta, TNF-alpha, CCL2 and CCL3 mRNA expressions in the olfactory bulb, not in the hippocampus of mice. To investigate the effect of a single administration of nanoparticles on neurotransmitters and proinflammatory cytokines in a mouse olfactory bulb, we performed in vivo microdialysis and real-time PCR methods. Ten-week-old male BALB/c mice were implanted with guide cannula in the right olfactory bulb and, I week later, were instilled vehicle or CB (14 nm, 250 mu g) intranasally. Six hours after the nanoparticle instillation, the mice were intraperitoneally injected with normal saline or 50 mu g of bacteria cell wall component lipoteichoic acid (LTA), which may potentiate CB-induced neurologic effect. Extracellular glutamate and glycine levels were significantly increased in the olfactory bulb of CB-instilled mice when compared with vehicle-instilled control mice. Moreover, we found that LTA further increased glutamate and glycine levels. However, no alteration of taurine and GABA levels was observed in the olfactory bulb of the same mice. We also detected immunological changes in the olfactory bulb 11 h after vehicle or CB instillation and found that IL- 1 beta mRNA expression was significantly increased in CB- and LTA-treated mice when compared with control group. However, TNF-alpha mRNA expression was increased significantly in CB- and saline-treated mice when compared with control group. These findings suggest that nanoparticle CB may modulate the extracellular amino acid neurotransmitter levels and proinflammatory cytokine IL-1 beta mRNA expressions synergistically with LTA in the mice olfactory bulb. (c) 2007 Elsevier Inc. All rights reserved.