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N-Acetylcysteine Reverses Anxiety and Oxidative Damage Induced by Unpredictable Chronic Stress in Zebrafish

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Abstract

There is accumulating evidence on the use of N-acetylcysteine (NAC) in the treatment of patients with neuropsychiatric disorders. As a multi-target drug and a glutathione precursor, NAC is a promising molecule in the management of stress-related disorders, for which there is an expanding field of research investigating novel therapies targeting oxidative pathways. The deleterious effects of chronic stress in the central nervous system are a result of glutamatergic hyperactivation, glutathione (GSH) depletion, oxidative stress, and increased inflammatory response, among others. The aim of this study was to investigate the effects of NAC in zebrafish submitted to unpredictable chronic stress (UCS). Animals were initially stressed or not for 7 days, followed by treatment with NAC (1 mg/L, 10 min) or vehicle for 7 days. UCS decreased the number of entries and time spent in the top area in the novel tank test, which indicate increased anxiety levels. It also increased reactive oxygen species (ROS) levels and lipid peroxidation (TBARS) while decreased non-protein thiols (NPSH) and superoxide dismutase (SOD) activity. NAC reversed the anxiety-like behavior and oxidative damage observed in stressed animals. Additional studies are needed to investigate the effects of this agent on glutamatergic modulation and inflammatory markers related to stress. Nevertheless, our study adds to the existing body of evidence supporting the clinical evaluation of NAC in mood disorders, anxiety, post-traumatic stress disorder, and other conditions associated with stress.

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Acknowledgements

R.M and M.M are recipients of fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq, Proc. 401162/2016-8 and 302800/2017-4) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Proc. 17/2551-0000974-6).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, ICBS, Universidade Federal do Rio Grande do Sul. (UFRGS), Rua Sarmento Leite, 500/305, Porto Alegre, RS, 90050170, Brazil

    Ricieri Mocelin, Matheus Marcon, Simone D’ambros, Juliane Mattos, Adrieli Sachett & Angelo Piato

  2. Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500/305, Porto Alegre, RS, 90050170, Brazil

    Ana P. Herrmann

  3. Programa de Pós-graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Avenida Senador Atílio Fontana, 591E, Chapecó, SC, 89809-000, Brazil

    Anna M. Siebel

  4. Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA, 70458, USA

    Angelo Piato

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  1. Ricieri Mocelin
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Mocelin, R., Marcon, M., D’ambros, S. et al. N-Acetylcysteine Reverses Anxiety and Oxidative Damage Induced by Unpredictable Chronic Stress in Zebrafish. Mol Neurobiol 56, 1188–1195 (2019). https://doi.org/10.1007/s12035-018-1165-y

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