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应用转录组分析了解过氧化氢暴露对鲤鱼(Cyprinus carpio)大脑功能的不良影响。

Application of transcriptome analysis to understand the adverse effects of hydrogen peroxide exposure on brain function in common carp (Cyprinus carpio).

机构信息

Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China; International Joint Research Laboratory for Fish Immunopharmacology, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.

Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.

出版信息

Environ Pollut. 2021 Oct 1;286:117240. doi: 10.1016/j.envpol.2021.117240. Epub 2021 May 13.

Abstract

Hydrogen peroxide (HO), as a common disinfectant, has been extensively used in aquaculture. The toxicity of high ambient HO for gills and liver of fish has received attention from many researchers. However, whether HO exposure induced brain injury and neurotoxicity has not been reported in fish. Therefore, this study aimed to explore the potential mechanism of HO toxicity in brain of common carp via transcriptome analysis and biochemical parameter detection. The fish were exposed to 0 (control) and 1 mM of HO for 1 h per day lasting 14 days. The results showed that HO exposure caused oxidative damage in brain evidenced by decreased glutathione (GSH), total antioxidant capacity (T-AOC) and nicotinamide adenine dinucleotide (NAD) levels, and increased formation of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Meanwhile, HO exposure reduced 5-hydroxytryptamine (5-HT) level, and down-regulated tryptophan hydroxylase 1 (tph1a), tph2, 5-hydroxytryptamine receptor 1A-beta (htr1ab) and htr2b expression in brain. Transcriptome analysis showed that HO exposure up-regulated 604 genes and down-regulated 1209 genes in brain. Go enrichment displayed that the differently expressed genes (DEGs) were enriched mainly in cellular process, single-organism process, metabolic process, and biological regulation in the biological process category. Further, KEGG enrichment indicated that HO exposure led to dysregulation of neurotransmitter signals including depression of glutamatergic synapse, GABAergic synapse and endocannabinoid signaling. Also, we found the alteration of three key pathways including calcium, cAMP and HIF-1 in brain after HO exposure. In conclusion, our data indicated that HO exposure induced oxidative damage and neurotoxicity, possibly related to dysregulation of neurotransmitters and calcium, cAMP and HIF-1 signaling pathways, which may adversely affect learning, memory and social responses of common carp. This study provided novel insight into biological effects and underlying mechanism of HO toxicity in aquatic animal, and contributed to proper application of HO in aquaculture.

摘要

过氧化氢(HO)作为一种常见的消毒剂,在水产养殖中得到了广泛的应用。高环境 HO 对鱼类鳃和肝脏的毒性已经引起了许多研究人员的关注。然而,HO 暴露是否会导致鱼类大脑损伤和神经毒性尚未有报道。因此,本研究旨在通过转录组分析和生化参数检测来探讨 HO 对鲤鱼大脑毒性的潜在机制。将鱼暴露于 0(对照)和 1 mM 的 HO 中,每天 1 小时,持续 14 天。结果表明,HO 暴露导致大脑氧化损伤,表现为谷胱甘肽(GSH)、总抗氧化能力(T-AOC)和烟酰胺腺嘌呤二核苷酸(NAD)水平降低,丙二醛(MDA)和 8-羟基-2'-脱氧鸟苷(8-OHdG)形成增加。同时,HO 暴露降低了 5-羟色胺(5-HT)水平,并下调了大脑中色氨酸羟化酶 1(tph1a)、tph2、5-羟色胺受体 1A-beta(htr1ab)和 htr2b 的表达。转录组分析显示,HO 暴露使大脑中 604 个基因上调,1209 个基因下调。GO 富集显示,差异表达基因(DEGs)在生物学过程类别中主要富集在细胞过程、单个生物体过程、代谢过程和生物调节。进一步的 KEGG 富集表明,HO 暴露导致神经递质信号失调,包括谷氨酸能突触、GABA 能突触和内源性大麻素信号的抑制。此外,我们发现 HO 暴露后大脑中钙、cAMP 和 HIF-1 三个关键途径发生改变。总之,我们的数据表明,HO 暴露导致氧化损伤和神经毒性,可能与神经递质和钙、cAMP 和 HIF-1 信号通路的失调有关,这可能对鲤鱼的学习、记忆和社交反应产生不利影响。本研究为 HO 在水生动物中的毒性的生物学效应和潜在机制提供了新的见解,并为 HO 在水产养殖中的合理应用提供了依据。

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