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Decrease in the Activity of Striatal-Enriched Protein-Tyrosine-Phosphatase (STEP) in the Brain of Danio rerio Treated with p-Chlorophenylalanine and Pargyline

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Abstract—

Fundamental neurophysiological processes are often studied using Danio rerio fish as a model. A selective inhibitor of striatal-enriched protein tyrosine phosphatase (STEP) reduces serotonin metabolism in the D. rerio brain. Both STEP and serotonin are involved in the development of neurodegenerative behavioral disorders. Reduction or elevation of the serotonin level in the brain of mice caused by the administration of p-chlorophenylalanine or pargyline, respectively, results in a decrease in the level of рtpn5 mRNA in the striatum, рtpn5 being the gene encoding STEP. However, it has not been established whether this occurs in other organisms. We studied the effect of inhibitors of synthesis (p-chlorophenylalanine) and degradation (pargyline) of serotonin on the expression of the ptpn5 gene and the activity of STEP in the brain of D. rerio. The fish were placed in water containing p-chlorophenylalanine (2 mg/L) or pargyline (0.5 mg/L) for 72 hours, and control subjects were kept in aquarium water. The p-chlorophenylalanine treatment decreased the serotonin level in the brain fourfold, whereas pargyline increased the level of this transmitter sixfold. Both p-chlorophenylalanine and pargyline decrease STEP activity in the D. rerio brain, without affecting the level of the рtpn5 mRNA gene. Thus, interaction between STEP and the serotonin system is observed in both mammals and fish, which indicates the similarity of the regulation processes in vertebrates.

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ACKNOWLEDGEMENTS

The authors are grateful to the fellows of the laboratory of physiologically active substances N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, for kindly granting the TC-2153 substance.

Funding

The study was supported by Budgetary project no. 0259-2021-0015.

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Authors and Affiliations

  1. Federal research center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

    E. A. Kulikova, D. V. Fursenko, E. Yu. Bazhenova & A. V. Kulikov

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  1. E. A. Kulikova
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  2. D. V. Fursenko
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  3. E. Yu. Bazhenova
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  4. A. V. Kulikov
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Correspondence to E. A. Kulikova.

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Statement on the welfare of animals. All procedures performed in this work correspond to the ethical standards of the institutional committee for research ethics and the Helsinki Declaration of 1964 and its following changes or comparable ethical norms.

Conflict of interests. The authors declare no conflict of interests.

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Abbreviations: 5-HT, serotonin; ptpn5, STEP protein-encoding gene; pol2e, DNA-dependent RNA polymerase; STEP, Striatal-Enriched protein tyrosine Phosphatase; MAO, monoamine oxidase; TPH2, tryptophanhydroxilase 2.

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Kulikova, E.A., Fursenko, D.V., Bazhenova, E.Y. et al. Decrease in the Activity of Striatal-Enriched Protein-Tyrosine-Phosphatase (STEP) in the Brain of Danio rerio Treated with p-Chlorophenylalanine and Pargyline. Mol Biol 55, 604–609 (2021). https://doi.org/10.1134/S0026893321020254

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  • DOI: https://doi.org/10.1134/S0026893321020254

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