Cholinergic System and Oxidative Stress Changes in the Brain of a Zebrafish Model Chronically Exposed to Ethanol
Cholinergic System and Oxidative Stress Changes in the Brain of a Zebrafish Model Chronically Exposed to Ethanol
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DOI：
10.1007/s12640-017-9816-8
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发表时间：
2018-05-01
影响因子：
3.7
通讯作者：
Rico, Eduardo Pacheco
中科院分区：
文献类型：
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作者：
Agostini, Jotele Fontana;Zuehl Dal Toe, Helena Cristina;Rico, Eduardo Pacheco
乙醇是一种广泛使用的药物，过量甚至适度的乙醇消费与几种神经递质系统的变化有关，包括胆碱能系统。酒精性痴呆的发病率及其损伤得到了多项研究的支持，尽管神经毒性的机制仍然知之甚少。考虑到斑马鱼具有完整的中枢神经系统（CNS），并且已经在斑马鱼中鉴定了几种信号系统，因此该神经毒理学模型变得有用。在本研究中，我们调查了长期的影响，乙醇消费对胆碱能系统，氧化应激，并在斑马鱼大脑的炎症参数。将动物暴露于0.5%（v/v）乙醇中7、14和28天。乙醇抑制胆碱乙酰转移酶的活性后7和14天，但不超过28天。乙酰胆碱酯酶活性在任何接触期后都没有变化。当与对照组相比，硫代巴比妥酸反应物种和二氯二氢荧光素水平增加后，慢性乙醇暴露。慢性乙醇暴露后，CAT/SOD比值促进的抗氧化活性发生改变，表明乙醇可诱导斑马鱼脑的氧化损伤。相反，硝酸盐和亚硝酸盐水平和巯基含量没有改变。乙醇并没有改变斑马鱼大脑中炎性细胞因子il-1b、il-10或tnf-alpha的基因表达。因此，胆碱能系统和氧化平衡是慢性乙醇毒性的目标。这种神经化学调节机制可能在理解斑马鱼模型研究中长期乙醇消耗和耐受性的影响方面发挥重要作用。
Ethanol is a widely used drug, and excess or even moderate consumption of ethanol is associated with changes in several neurotransmitter systems, including the cholinergic system. The incidence of alcoholic dementia and its insults are well supported by multiple studies, although the mechanisms of neurotoxicity are still poorly understood. Considering that zebrafish have a complete central nervous system (CNS) and that several signaling systems have already been identified in zebrafish, this neurotoxicological model has become useful. In the present study, we investigated the long-term effects of ethanol consumption on the cholinergic system, on oxidative stress, and on inflammatory parameters in the zebrafish brain. Animals were exposed to 0.5% (v/v) ethanol for 7, 14, and 28 days. Ethanol inhibited choline acetyltransferase activity after 7 and 14 days but not after 28 days. Acetylcholinesterase activity did not change after any of the exposure periods. When compared to the control group, thiobarbituric acid reactive species and dichlorodihydrofluorescein levels were increased after chronic ethanol exposure. Antioxidant activity promoted by the CAT/SOD ratio was altered after chronic ethanol exposure, suggesting that EtOH can induce oxidative damage in the zebrafish brain. In contrast, nitrate and nitrite levels and sulfhydryl content were not altered. Ethanol did not modify gene expression of the inflammatory cytokines il-1b, il-10, or tnf-alpha in the zebrafish brain. Therefore, the cholinergic system and the oxidative balance were targeted by chronic ethanol toxicity. This neurochemical regulatory mechanism may play an important role in understanding the effects of long-term ethanol consumption and tolerance in zebrafish model studies.