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Cholinergic System and Oxidative Stress Changes in the Brain of a Zebrafish Model Chronically Exposed to Ethanol

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Abstract

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-α 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.

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Acknowledgements

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Fundação de Amparo à Pesquisa do Estado de Santa Catarina (FAPESC), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Universidade do Extremo Sul Catarinense (UNESC).

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Rico had full access to all study data and takes responsibility for the data integrity and analysis accuracy.

Concept and design: Agostini, Dal Toé, Cruz, and Rico.

Data acquisition: Agostini, Dal Toé, Vieira, Baldin, Cruz, Longo, and Machado.

Data analysis and interpretation: Agostini, Cruz, Longo, Machado, and Rico.

Manuscript drafting: Baldin, Cruz, Longo, Machado, and Silveira.

Manuscript critical revisions for important intellectual content: Agostini, Dal Toé, Cruz, and Rico, Naithan Ludian Fernandes Costa.

Administrative, technical, or material support: Schuck, Silveira, and Rico.

Study supervision: Rico.

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Correspondence to Eduardo Pacheco Rico.

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The Ethics Committee of the University of Southern Santa Catarina (UNESC) has approved the present study.

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Agostini, J.F., Toé, H.C.Z.D., Vieira, K.M. et al. Cholinergic System and Oxidative Stress Changes in the Brain of a Zebrafish Model Chronically Exposed to Ethanol. Neurotox Res 33, 749–758 (2018). https://doi.org/10.1007/s12640-017-9816-8

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