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Pargyline and р-Chlorophenylalanine Decrease Expression of Ptpn5 Encoding Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in the Mouse Striatum

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Abstract

Striatal-enriched protein tyrosine phosphatase (STEP), which was initially identified in the striatum, is encoded by the Ptpn5 gene and is expressed in neurons of various structures of the brain. STEP is involved in regulating neuroplasticity, and its expression abnormalities are associated with human neurodegenerative disorders. The STEP inhibitor 8-trifluoromethyl-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153) has been shown to affect the serotoninergic system of the brain. However, the influence of the serotoninergic system on the STEP regulation has not been studied yet. The aim of the study was to investigate how pharmacologically induced changes in the brain serotonin (5-HT) level affect Ptpn5 expression and STEP activity in adult male C57BL/6J mice. To modulate the 5-HT level in the brain, the 5-HT synthesis inhibitor p-chlorophenylalanine or 5-HT degradation inhibitor pargyline was administered intraperitoneally for three successive days. Changes in 5-HT concentration in the brain were assayed using high-performance liquid chromatography. The STEP activity was determined spectrophotometrically in the supernatant by the rate of p-nitrophenyl phosphate dephosphorylation in the absence and presence of the selective STEP inhibitor TC-2153. The Ptpn5 mRNA level was determined using quantitative RT-PCR. The Ptpn5 expression level in the striatum was three times higher than in the cortex and hippocampus. Both increases and decreases in brain 5-HT were for the first time associated with a decrease in Ptpn5 mRNA in the striatum. STEP activity in the striatum and cortex was significantly higher than in the hippocampus. However, p-chlorophenylalanine and pargyline did not affect the STEP activity in the brain structures tested. Thus, a new method was proposed to study the STEP activity in the brain and p-chlorophenylalanine and pargyline were shown to decrease Ptpn5 expression in the striatum in mice.

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ACKNOWLEDGMENTS

We are grateful to researchers of the Laboratory of Physiologically Active Compounds (headed by Doct. Sci. (chem.), Prof. N.F. Salakhutdinov) of the Vorozhtsov Novosibirsk Institute of Organic Chemistry (Siberian Branch, Russian Academy of Sciences) for kindly providing TC-2153.

Funding

This work was supported by the Russian Science Foundation (project no. 17-15-01032). The breeding and rearing of animals were supported by a budgetary program for young researchers (project no. 0259-2019-0002) and were carried out using equipment of the Collective Access Center of Genetic Resources of Laboratory Animals (Institute of Cytology and Genetics), which was supported by the Ministry of Education and Science of the Russian Federation (unique project identifier RFMEFI62119X0023).

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  1. Institute of Cytology and Genetics, Siberian Branch, 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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Statement on the welfare of animals. Animal rearing conditions and experimental procedures followed the guidelines established by The Directive 2010/63/EU of the European Parliament and the Council of 22 September 2010 and were approved by the Ethics Committee at the Institute of Cytology and Genetics.

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Translated by T. Tkacheva

Abbreviations: 5-HT, serotonin; Ptpn5, the STEP gene; Polr2a, DNA-directed RNA polymerase II; STEP, striatal-enriched protein tyrosine phosphatase; MAOA, monoamine oxidase A; TPH2, tryptophan hydroxylase 2.

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Kulikova, E.A., Fursenko, D.V., Bazhenova, E.Y. et al. Pargyline and р-Chlorophenylalanine Decrease Expression of Ptpn5 Encoding Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in the Mouse Striatum. Mol Biol 54, 274–280 (2020). https://doi.org/10.1134/S0026893320020090

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