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The Role of C1473G Polymorphism in Mouse Triptophan Hydroxylase 2 Gene in the Acute Effects of Ethanol on the c-fos Gene Expression and Metabolism of Biogenic Amines in the Brain

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Abstract

Tryptophan hydroxylase 2 is a key enzyme in the synthesis of the neurotransmitter serotonin, which plays an important role in the regulation of behavior and various physiological functions. We studied the effect of acute ethanol administration on the expression of the early response c-fos gene and metabolism of serotonin and catecholamines in the brain structures of B6-1473C and B6-1473G congenic mouse strains differing in the single-nucleotide substitution C1473G in the Tph2 gene and activity of the encoded enzyme. Acute alcoholization led to a significant upregulation of the c-fos gene expression in the frontal cortex and striatum of B6-1473G mice and in the hippocampus of B6-1473C mice and caused a decrease in the index of serotonin metabolism in the nucleus accumbens in B6-1473C mice and in the hippocampus and striatum of B6-1473G mice, as well as to the decrease in the norepinephrine level in the hypothalamus of B6-1473C mice. Therefore, the C1473G polymorphism in the Tph2 gene has a significant effect of acute ethanol administration on the c-fos expression pattern and metabolism of biogenic amines in the mouse brain.

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Abbreviations

5-HT:

serotonin

DA:

dopamine

DOPAC:

3,4-dihydroxyphenylacetic acid

HVA:

homovanillic acid

NE:

norepinephrine

TPH2:

tryptophan hydroxylase

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Funding

This work was supported by the Russian Science Foundation (project no. 21-15-00051). The animals’ maintenance was funded by a Budget Project FWNR-2022-0023.

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Authors and Affiliations

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

    Darya V. Bazovkina, Dariya V. Fursenko, Vladimir S. Naumenko & Aleksandr V. Kulikov

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  1. Darya V. Bazovkina
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  2. Dariya V. Fursenko
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  3. Vladimir S. Naumenko
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  4. Aleksandr V. Kulikov
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Contributions

D.V.B. and A.V.K. developed the concept, supervised the study, and discussed the results; D.V.B., D.V.F., and V.S.N. carried out the experiments; D.V.B. wrote the manuscript.

Corresponding author

Correspondence to Darya V. Bazovkina.

Ethics declarations

The authors declare no conflict of interest. All procedures were performed in compliance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications no. 80023, 1996) and the order no. 119 from 01.04.2016 “On the establishment of rules for the proper laboratory practice” (no. 43232, registered on 15.08.2016) by the Ministry of Health of the Russian Federation. The experiments and animal maintenance procedures were approved by the Bioethics Committee of the Institute of Cytology and Genetics.

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Bazovkina, D.V., Fursenko, D.V., Naumenko, V.S. et al. The Role of C1473G Polymorphism in Mouse Triptophan Hydroxylase 2 Gene in the Acute Effects of Ethanol on the c-fos Gene Expression and Metabolism of Biogenic Amines in the Brain. Biochemistry Moscow 88, 291–302 (2023). https://doi.org/10.1134/S000629792303001X

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