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Long-Term Methionine Exposure Induces Memory Impairment on Inhibitory Avoidance Task and Alters Acetylcholinesterase Activity and Expression in Zebrafish (Danio rerio)

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Abstract

Hypermethioninemic patients exhibit a variable degree of neurological dysfunction. However, the mechanisms involved in these alterations have not been completely clarified. Cholinergic system has been implicated in many physiological processes, including cognitive performances, as learning, and memory. Parameters of cholinergic signaling have already been characterized in zebrafish brain. Since zebrafish is a small freshwater teleost which is a vertebrate model for modeling behavioral and functional parameters related to human pathogenesis and for clinical treatment screenings, in the present study we investigated the effects of short- and long-term methionine exposure on cognitive impairment, AChE activity and gene expression in zebrafish. For the studies, animals were exposed at two methionine concentrations (1.5 and 3.0 mM) during 1 h or 7 days (short- or long-term treatments, respectively). We observed a significant increase in AChE activity of zebrafish brain membranes after long-term methionine exposure at 3.0 mM. However, AChE gene expression decreased significantly in both concentrations tested after 7 days of treatment, suggesting that post-translational events are involved in the enhancement of AChE activity. Methionine treatment induces memory deficit in zebrafish after long-term exposure to this amino acid, which could be related, at least in part, with cognitive impairment observed in hypermethioninemia. Therefore, the results here presented raise a new perspective to use the zebrafish as a complementary vertebrate model for studying inborn errors of metabolism, which may help to better understand the pathophysiology of this disease.

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Acknowledgments

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

Conflict of interest

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil

    Fernanda Cenci Vuaden, Luiz Eduardo B. Savio & Angela T. S. Wyse

  2. Departamento Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil

    Angelo L. Piato, Talita C. Pereira, Mônica R. Vianna, Maurício R. Bogo & Carla D. Bonan

  3. Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, RS, 90035-003, Brazil

    Mônica R. Vianna, Maurício R. Bogo & Carla D. Bonan

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  1. Fernanda Cenci Vuaden
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  2. Luiz Eduardo B. Savio
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  3. Angelo L. Piato
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  8. Angela T. S. Wyse
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Correspondence to Fernanda Cenci Vuaden or Angela T. S. Wyse.

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Vuaden, F.C., Savio, L.E.B., Piato, A.L. et al. Long-Term Methionine Exposure Induces Memory Impairment on Inhibitory Avoidance Task and Alters Acetylcholinesterase Activity and Expression in Zebrafish (Danio rerio). Neurochem Res 37, 1545–1553 (2012). https://doi.org/10.1007/s11064-012-0749-6

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  • DOI: https://doi.org/10.1007/s11064-012-0749-6

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