Gholamine Babak, Karimi Isaac, Salimi Amir, Mazdarani Parisa, Becker Lora A
1 Department of Pharmacology, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Islamic Republic of Iran.
2 Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran.
Toxicol Ind Health. 2017 Apr;33(4):340-350. doi: 10.1177/0748233716644381. Epub 2016 Jul 9.
The aim of this study was to evaluate neurobehavioral toxicity of single-walled (SWNTs) and multiwalled carbon nanotubes (MWNTs) in mice.
Male NMRI mice were randomized into 5 groups ( n = 10 each): Normal control (NC) group was injected intraperitoneally (i.p.) with phosphate-buffered saline (PBS) solution (pH 7.8; ca. 1 mL), MW80 and MW800 groups were injected with either i.p. 80 or 800 mg kg MWNTs suspended in 1 mL of PBS and SW80 and SW800 groups were injected with either i.p. 80 or 800 mg kg SWNTs suspended in 1 mL of PBS. After 2 weeks, five mice from each group were evaluated for brain-derived neurotrophic factor (BDNF) messenger RNA expression and protein content of brain tissues. Locomotion, anxiety, learning and memory, and depression were measured by open field test (OFT), elevated plus-maze (EPM), object recognition test (ORT), and forced swimming test (FST), respectively.
Ambulation time and center arena time in the OFT did not change among groups. In the EPM paradigm, SWNTs (800 mg kg) and MWNTs (80 and 800 mg kg) showed an anxiogenic effect. In ORT, MWNTs (80 mg kg) increased the discrimination ratio while in FST, MWNTs showed a depressant effect as compared to vehicle. The BDNF gene expression in mice treated with 80 and 800 mg kg SWNTs or 80 mg kg MWNTs decreased as compared to NC mice although BDNF gene expression increased in mice that were treated with 800 mg kg MWNTs. The whole brain BDNF protein content did not change among groups.
Our study showed that i.p. exposure to carbon nanotubes (CNTs) may result in behavioral toxicity linked with expression of depression or anxiety that depends on the type of CNTs. In addition, exposure to CNTs changed BDNF gene expression.
本研究旨在评估单壁碳纳米管（SWNTs）和多壁碳纳米管（MWNTs）对小鼠的神经行为毒性。
将雄性NMRI小鼠随机分为5组（每组n = 10）：正常对照组（NC）腹腔注射磷酸盐缓冲盐水（PBS）溶液（pH 7.8；约1 mL），MW80组和MW800组分别腹腔注射悬浮于1 mL PBS中的80或800 mg/kg MWNTs，SW80组和SW800组分别腹腔注射悬浮于1 mL PBS中的80或800 mg/kg SWNTs。2周后，每组取5只小鼠评估脑组织中脑源性神经营养因子（BDNF）信使核糖核酸表达和蛋白质含量。分别通过旷场试验（OFT）、高架十字迷宫试验（EPM）、物体识别试验（ORT）和强迫游泳试验（FST）测量运动能力、焦虑、学习和记忆以及抑郁情况。
OFT中的行走时间和中央区域时间在各组间无变化。在EPM范式中，SWNTs（800 mg/kg）和MWNTs（80和800 mg/kg）显示出致焦虑作用。在ORT中，MWNTs（80 mg/kg）提高了辨别率，而在FST中，与溶剂对照组相比MWNTs显示出抑制作用。与NC小鼠相比，接受80和800 mg/kg SWNTs或80 mg/kg MWNTs处理的小鼠中BDNF基因表达降低，尽管接受800 mg/kg MWNTs处理的小鼠中BDNF基因表达增加。各组间全脑BDNF蛋白质含量无变化。
我们的研究表明，腹腔注射碳纳米管（CNTs）可能导致与抑郁或焦虑表达相关的行为毒性，这取决于CNTs的类型。此外，接触CNTs会改变BDNF基因表达。
