溴氰菊酯对斑马鱼早期发育阶段的神经毒性研究
Neurotoxicity of Deltamethrin on Zebrafish in Early Developmental Stage
-
摘要: 溴氰菊酯(deltamethrin, DM)作为Ⅱ型拟除虫菊酯杀虫剂已被广泛使用，高度的亲脂性可以使其轻易通过血脑屏障作用于神经系统，但其对斑马鱼早期神经发育的影响及毒性机制仍不清楚。本研究以斑马鱼(Danio rerio)胚胎为研究对象，分别暴露于0、10、20、50 μg·L-1的DM中，对暴露后胚胎的发育状况、运动能力等分析后，进一步利用转基因斑马鱼从神经细胞发育方面评估DM对斑马鱼早期发育阶段的神经毒性。结果显示，从3 hpf开始暴露，在24 hpf，50 μg·L-1暴露组自发卷尾运动频率相较于对照组降低了约41.2%(P<0.001)；在36 hpf，各暴露组胚胎孵化率均升高，20、50 μg·L-1暴露组心率显著升高(P<0.01，P<0.0001)，体长显著短于对照组(P<0.01)，这些结果显示出DM对胚胎发育的影响于其浓度之间具有明显剂量依赖效应。通过对斑马鱼幼鱼的自发运动、光暗行为和旷场行为的分析，发现暴露后斑马鱼幼鱼在3种情景中运动行为均变得迟缓，表明DM暴露影响斑马鱼运动能力，且对外界环境刺激的响应能力以及主动探索新环境的能力均减弱。进一步通过对神经系统特异性标记的转基因斑马鱼品系的研究发现，DM暴露导致斑马鱼神经干/祖细胞数目显著减少(P<0.01，P<0.001)，神经元细胞活性加强，且凋亡细胞数目显著增多(P<0.0001)。结果表明，溴氰菊酯在斑马鱼发育早期的毒性与其影响神经细胞的活性相关。DM通过破坏神经干/祖细胞的数量、过度激活神经元和促进神经细胞凋亡等方面对斑马鱼中枢神经系统产生毒性，进而影响斑马鱼胚胎的运动行为。Abstract: Deltamethrin (DM) has been widely used as a type II pyrethroid insecticide. Its high lipophilicity allows it to easily pass through the blood-brain barrier and affect the nervous system. However, its impact on the early neural development of zebrafish and the mechanism of toxicity remains unclear. In this study, zebrafish (Danio rerio) embryos were exposed to DM with different concentration of 0, 10, 20 and 50 μg·L-1 to analyze the development and movement ability. The neurotoxicity of DM to zebrafish larvae was evaluated on the development of the nerve cells of transgenic zebrafish line. The results showed that the frequency of spontaneous coiling decreased 41.2% (P<0.001) by 50 μg·L-1 DM exposure at 24 hpf. The hatching rate of all the DM exposure groups was higher than the control group and heart rate were significantly increased in 20 and 50 μg·L-1 groups (P<0.01, P<0.0001), and the body length was significantly reduced (P<0.01) at 36 hpf. These results showed that the effect of DM on embryo development was dose-dependent. Through the analysis of the spontaneous swim, light-dark stimulus and open field behavior of zebrafish larvae, it was found that zebrafish larvae became sluggish in those three scenarios, indicating that DM exposure affected the mobility of zebrafish, and the ability to respond to external environmental stimuli and the ability to actively explore new environments was weakened. Further analysis of transgenic zebrafish strains with specific markers for neural cell systems found that DM exposure caused a significant decrease in the number of nerve stem/progenitor cells in zebrafish (P<0.01, P<0.001), neuronal cell activity was enhanced, and the number of apoptotic cells was significantly increased (P<0.0001). The results suggested that the neurotoxicity of zebrafish larvae induced by DM is related to the nerve cell viability. DM is toxic to the central nervous system of zebrafish by destroying the number of nerve stem / progenitor cells, over-activating neurons and promoting apoptosis of nerve cells, thus affecting the behavior of zebrafish embryos and larvae.
-
Key words:
- deltamethrin /
- zebrafish /
- neurotoxicity /
- ethology
-
-
Anadón A, Arés I, Martínez M A, et al. Pyrethrins and Synthetic Pyrethroids: Use in Veterinary Medicine [M]//Ramawat K, Mérillon J M. Natural Products. Berlin, Heidelberg: Springer, 2013: 4061-4086 宋雪英, 刘伟健, 孙百惠, 等. 溴氰菊酯的急性毒性效应与毒性机理研究进展[J]. 沈阳大学学报(自然科学版), 2020, 32(1): 13-19 Song X Y, Liu W J, Sun B H, et al. Advances in study of acute toxicity effects and toxicity mechanisms of deltamethrin [J]. Journal of Shenyang University (Natural Science), 2020, 32(1): 13-19(in Chinese) Ullah S, Li Z Q, Ul Arifeen M Z, et al. Multiple biomarkers based appraisal of deltamethrin induced toxicity in silver carp (Hypophthalmichthys molitrix) [J]. Chemosphere, 2019, 214: 519-533 国家市场监督管理总局, 国家标准化管理委员会. 生活饮用水卫生标准: GB 5749—2022[S]. 北京: 中国标准出版社, 2020 Andersen H R, David A, Freire C, et al. Pyrethroids and developmental neurotoxicity: A critical review of epidemiological studies and supporting mechanistic evidence [J]. Environmental Research, 2022, 214(Pt 2): 113935 Wang N, Huang M Y, Guo X Y, et al. Urinary metabolites of organophosphate and pyrethroid pesticides and neurobehavioral effects in Chinese children [J]. Environmental Science & Technology, 2016, 50(17): 9627-9635 Elser B A, Hing B, Stevens H E. A narrative review of converging evidence addressing developmental toxicity of pyrethroid insecticides [J]. Critical Reviews in Toxicology, 2022, 52(5): 371-388 Pitzer E M, Williams M T, Vorhees C V. Effects of pyrethroids on brain development and behavior: Deltamethrin [J]. Neurotoxicology and Teratology, 2021, 87: 106983 Vellingiri B, Chandrasekhar M, Sri Sabari S, et al. Neurotoxicity of pesticides: A link to neurodegeneration [J]. Ecotoxicology and Environmental Safety, 2022, 243: 113972 Lu Q R, Sun Y Q, Ares I, et al. Deltamethrin toxicity: A review of oxidative stress and metabolism [J]. Environmental Research, 2019, 170: 260-281 Field L M, Emyr Davies T G, O’Reilly A O, et al. Voltage-gated sodium channels as targets for pyrethroid insecticides [J]. European Biophysics Journal, 2017, 46(7): 675-679 Ullah S, Li Z Q, Zuberi A, et al. Biomarkers of pyrethroid toxicity in fish [J]. Environmental Chemistry Letters, 2019, 17(2): 945-973 Hossain M M, Liu J, Richardson J R. Pyrethroid insecticides directly activate microglia through interaction with voltage-gated sodium channels [J]. Toxicological Sciences: An Official Journal of the Society of Toxicology, 2017, 155(1): 112-123 Chrustek A, Hołyńska-Iwan I, Dziembowska I, et al. Current research on the safety of pyrethroids used as insecticides [J]. Medicina, 2018, 54(4): 61 Goyal R, Spencer K A, Borodinsky L N. From neural tube formation through the differentiation of spinal cord neurons: Ion channels in action during neural development [J]. Frontiers in Molecular Neuroscience, 2020, 13: 62 Shen H Y, Bocksteins E, Kondrychyn I, et al. Functional antagonism of voltage-gated K+ channel α-subunits in the developing brain ventricular system [J]. Development, 2016, 143(22): 4249-4260 Feriani A, Tir M, Hachani R, et al. Permethrin induced arterial retention of native and oxidized LDL in rats by promoting inflammation, oxidative stress and affecting LDL receptors, and collagen genes [J]. Ecotoxicology and Environmental Safety, 2021, 207: 111269 He B N, Wang X, Wei L, et al. β-cypermethrin and its metabolite 3-phenoxybenzoic acid induce cytotoxicity and block granulocytic cell differentiation in HL-60 cells [J]. Acta Biochimica et Biophysica Sinica, 2018, 50(8): 740-747 Olivares C I, Field J A, Simonich M, et al. Arsenic (Ⅲ, Ⅴ), indium (Ⅲ), and gallium (Ⅲ) toxicity to zebrafish embryos using a high-throughput multi-endpoint in vivo developmental and behavioral assay [J]. Chemosphere, 2016, 148: 361-368 MacRae C A, Peterson R T. Zebrafish as tools for drug discovery [J]. Nature Reviews Drug Discovery, 2015, 14(10): 721-731 Stewart A M, Braubach O, Spitsbergen J, et al. Zebrafish models for translational neuroscience research: From tank to bedside [J]. Trends in Neurosciences, 2014, 37(5): 264-278 Abe F R, Mendonça J N, Moraes L A, et al. Toxicological and behavioral responses as a tool to assess the effects of natural and synthetic dyes on zebrafish early life [J]. Chemosphere, 2017, 178: 282-290 Velki M, di Paolo C, Nelles J, et al. Diuron and diazinon alter the behavior of zebrafish embryos and larvae in the absence of acute toxicity [J]. Chemosphere, 2017, 180: 65-76 Hanigan D, Truong L, Simonich M, et al. Zebrafish embryo toxicity of 15 chlorinated, brominated, and iodinated disinfection by-products [J]. Journal of Environmental Sciences (China), 2017, 58: 302-310 卯明彩, 孟瑞媛, 李亚梦, 等. 环丙沙星对斑马鱼早期发育阶段的神经毒性研究[J]. 生态毒理学报, 2023, 18(4): 411-420 Mao M C, Meng R Y, Li Y M, et al. Neurotoxicity of ciprofloxacin on early life stages of Danio rerio [J]. Asian Journal of Ecotoxicology, 2023, 18(4): 411-420(in Chinese)
Tufi S, Leonards P, Lamoree M, et al. Changes in neurotransmitter profiles during early zebrafish (Danio rerio) development and after pesticide exposure [J]. Environmental Science & Technology, 2016, 50(6): 3222-3230 Xia S Y, Zhu X H, Yan Y P, et al. Developmental neurotoxicity of antimony (Sb) in the early life stages of zebrafish [J]. Ecotoxicology and Environmental Safety, 2021, 218: 112308 Chen J F, Li J N, Jiang H, et al. Developmental co-exposure of TBBPA and titanium dioxide nanoparticle induced behavioral deficits in larval zebrafish [J]. Ecotoxicology and Environmental Safety, 2021, 215: 112176 Liu X Y, Zhang Q P, Li S B, et al. Developmental toxicity and neurotoxicity of synthetic organic insecticides in zebrafish (Danio rerio): A comparative study of deltamethrin, acephate, and thiamethoxam [J]. Chemosphere, 2018, 199: 16-25 Pamanji R, Bethu M S, Yashwanth B, et al. Developmental toxic effects of monocrotophos, an organophosphorous pesticide, on zebrafish (Danio rerio) embryos [J]. Environmental Science and Pollution Research, 2015, 22(10): 7744-7753 Truong L, Gonnerman G, Simonich M T, et al. Assessment of the developmental and neurotoxicity of the mosquito control larvicide, pyriproxyfen, using embryonic zebrafish [J]. Environmental Pollution, 2016, 218: 1089-1093 Rosa J G S, Lima C, Lopes-Ferreira M. Zebrafish larvae behavior models as a tool for drug screenings and pre-clinical trials: A review [J]. International Journal of Molecular Sciences, 2022, 23(12): 6647 Vaz R, Hofmeister W, Lindstrand A. Zebrafish models of neurodevelopmental disorders: Limitations and benefits of current tools and techniques [J]. International Journal of Molecular Sciences, 2019, 20(6): 1296 Kinkhabwala A, Riley M, Koyama M, et al. A structural and functional ground plan for neurons in the hindbrain of zebrafish [J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(3): 1164-1169 Koyama M, Kinkhabwala A, Satou, et al. Mapping a sensory-motor network onto a structural and functional ground plan in the hindbrain [J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(3): 1170-1175 Randlett O, Wee C L, Naumann E A, et al. Whole-brain activity mapping onto a zebrafish brain atlas [J]. Nature Methods, 2015, 12(11): 1039-1046 Sands B, Mgidiswa N, Nyamukondiwa C, et al. Environmental consequences of deltamethrin residues in cattle feces in an African agricultural landscape [J]. Ecology and Evolution, 2018, 8(5): 2938-2946 Miao W Y, Jiang Y M, Hong Q Y, et al. Systematic evaluation of the toxicological effects of deltamethrin exposure in zebrafish larvae [J]. Environmental Toxicology and Pharmacology, 2023, 100: 104155 Liu X Y, Gao Q, Feng Z Y, et al. Protective effects of spermidine and melatonin on deltamethrin-induced cardiotoxicity and neurotoxicity in zebrafish [J]. Cardiovascular Toxicology, 2021, 21(1): 29-41 Li M, Liu X Y, Feng X Z. Cardiovascular toxicity and anxiety-like behavior induced by deltamethrin in zebrafish (Danio rerio) larvae [J]. Chemosphere, 2019, 219: 155-164 Boulanger-Weill J, Sumbre G. Functional integration of newborn neurons in the zebrafish optic tectum [J]. Frontiers in Cell and Developmental Biology, 2019, 7: 57 尚春峰, 穆宇, 杜久林. 以透明脑, 观澄明心: 斑马鱼神经功能研究进展[J]. 中国科学: 生命科学, 2015, 45(3): 223-236 Shang C F, Mu Y, Du J L. Zebrafish swimming into neuroscience research: A visible mind in a transparent brain [J]. Scientia Sinica Vitae, 2015, 45(3): 223-236(in Chinese)
Chueh T C, Hsu L S, Kao C M, et al. Transcriptome analysis of zebrafish embryos exposed to deltamethrin [J]. Environmental Toxicology, 2017, 32(5): 1548-1557 Kumar K, Patro N, Patro I. Impaired structural and functional development of cerebellum following gestational exposure of deltamethrin in rats: Role of reelin [J]. Cellular and Molecular Neurobiology, 2013, 33(5): 731-746 Yang Y, Wu N X, Wang C L. Toxicity of the pyrethroid bifenthrin insecticide [J]. Environmental Chemistry Letters, 2018, 16(4): 1377-1391 -
点击查看大图
计量
- 文章访问数: 1184
- HTML全文浏览数: 1184
- PDF下载数: 195
- 施引文献: 0
下载:
