Skip to main content
SpringerLink
Log in

Effect of the C1473G Polymorphic Variant of the Tryptophan Hydroxylase 2 Gene and Photoperiod Length on the Dopamine System of the Mouse Brain

  • GENOMICS. TRANSCRIPTOMICS
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract—

A decrease in the light in autumn and winter causes depression like seasonal affective disorders (SAD) in sensitive patients, in which the serotonin (5-HT) and dopamine (DA) brain mediator systems are involved. We studied the interaction of the 5-HT and DA brain systems in an experimental SAD model in sexually mature male mice of the congenic B6-1473C and B6-1473G lines with high and low activity of tryptophan hydroxylase 2, a key enzyme of 5-HT synthesis in the brain. Mice of each line (divided into two groups of eight individuals) were kept for 30 days in standard (14 h light/10 h dark) and short (4 h light/20 h dark) daylight. The presence of the C1473G variant in the tryptophan hydroxylase 2 gene did not affect the expression of key genes of DA system: Drd1, Drd2, Scl6a3, Th, and Comt, that encode the D1 and D2 receptors, dopamine transporter, tyrosine hydroxylase, and catechol-o-methyltransferase, respectively. A decrease in the level of DA in the midbrain, as well as of its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, was detected in B6-1473G mice. Keeping mice in short daylight did not affect expression of the Drd1 gene in all brain structures nor the expression of the Slc6a3 and Th genes in the midbrain. Drd2 expression increased in the midbrain and decreased in the hippocampus, where Comt expression increased. An increase in DA level in the midbrain and DOPAC in the striatum was detected in mice kept in short daylight. This indicates the involvement of the brain’s DA system in the reaction to a decrease in daylight duration. No statistically significant effect of the interaction between the presence of the C1473G variant and daylight length on indicators of the activity of DA system was detected. No reasons were found to assert that this polymorphism determines the observed reaction of the brain DA system in keeping of animals under short daylight conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. Rosenthal E., Sack D.A., Gillin J.C., Lewy A.J., Goodwin F.K., Davenport Y., Mueller P.S., Newsome D.A., Wehr T.A. 1984. Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch. Gen. Psychiatry. 41, 72‒80.

    Article  CAS  PubMed  Google Scholar 

  2. Levitan R.D. 2007. The chronobiology and neurobiology of winter seasonal affective disorder. Dialogues Clin. Neurosci. 9, 315–324.

    PubMed  PubMed Central  Google Scholar 

  3. Melrose S. 2015. Seasonal affective disorder: An overview of assessment and treatment approaches. Depress. Res. Treat. 2015, 178564.

    PubMed  PubMed Central  Google Scholar 

  4. Wirz-Justice A. 2018. Seasonality in affective disorders. Gen. Comp. Endocrinol.258, 244‒249.

    Article  CAS  PubMed  Google Scholar 

  5. Lam R.W., Levitan R.D. 2000. Pathophysiology of seasonal affective disorder: A review. J. Psychiatry Neurosci.25, 469‒480.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Neumeister A., Konstantinidis A., Praschak-Rieder N., Willeit M., Hilger E., Stastny J., Kasper S. 2001. Monoaminergic function in the pathogenesis of seasonal affective disorder. Int. J. Neuropsychopharmacol.4, 409‒420.

    Article  CAS  PubMed  Google Scholar 

  7. Cawley E.I., Park S., aan het Rot M., Sancton K., Benkelfat C., Young S.N., Boivin D.B., Leyton M. 2013. Dopamine and light: Dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder. J. Psychiatry Neurosci. 38, 388‒397.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gupta A., Sharma P.K., Garg V.K., Singh A.K., Mondal S.C. 2013. Role of serotonin in seasonal affective disorder. Eur. Rev. Med. Pharmacol. Sci.17, 49–55.

    CAS  PubMed  Google Scholar 

  9. Kulikov A.V., Popova N.K. 2015. Tryptophan hydroxylase 2 in seasonal affective disorder: Underestimated perspectives? Rev. Neurosci.26, 679–690.

    Article  CAS  PubMed  Google Scholar 

  10. Enoch M.A., Goldman D., Barnett R., Sher L., Mazzanti C.M., Rosenthal N.E. 1999. Association between seasonal affective disorder and the 5-HT2A promoter polymorphism, –1438G/A. Mol. Psychiatry.4, 89–92.

    Article  CAS  PubMed  Google Scholar 

  11. Arias B., Gutiérrez B., Pintor L., Gastó C., Fañanás L. 2001. Variability in the 5-HT(2A) receptor gene is associated with seasonal pattern in major depression. Mol. Psychiatry.6, 239–242.

    Article  CAS  PubMed  Google Scholar 

  12. Lee H.J., Sung S.M., Lim S.W., Paik J.W., Kim Leen. 2006. Seasonality associated with the serotonin 2A receptor –1438 A/G polymorphism. J. Affect. Disord. 95, 145–148.

    Article  CAS  PubMed  Google Scholar 

  13. Molnar E., Lazary J., Benko A., Gonda X., Pap D., Mekli K., Juhasz G., Kovacs G., Kurimay T., Rihmer Z., Bagdy G. 2010. Seasonality and winter-type seasonal depression are associated with the rs731779 polymorphism of the serotonin-2A receptor gene. Eur. Neuropsychopharmacol. 20, 655–662.

    Article  CAS  PubMed  Google Scholar 

  14. Levitan R.D., Masellis M., Basile V.S., Lam R.W., Kaplan A.S., Davis C., Muglia P., Mackenzie B., Tharmalingam S., Kennedy S.H., Macciardi F., Kennedy J.L. 2004. The dopamine-4 receptor gene associated with binge eating and weight gain in women with seasonal affective disorder: an evolutionary perspective. Biol. Psychiatry. 56, 665‒669.

    Article  CAS  PubMed  Google Scholar 

  15. Levitan R.D., Masellis M., Lam R.W., Muglia P., Basile V.S., Jain U., Kaplan A.S., Tharmalingam S., Kennedy S.H., Kennedy J.L. 2004b. Childhood inattention and dysphoria and adult obesity associated with the dopamine D4 receptor gene in overeating women with seasonal affective disorder. Neuropsychopharmacology.29, 179‒186.

    Article  CAS  PubMed  Google Scholar 

  16. Osipova D.V., Kulikov A.V., Popova N.K. 2009. C1473G polymorphism in mouse Tph2 gene is linked to tryptophan hydroxylase-2 activity in the brain, intermale aggression, and depressive-like behavior in the forced swim test. J. Neurosci. Res. 87, 1168–1174.

    Article  CAS  PubMed  Google Scholar 

  17. Bazovkina D.V., Lichman D.V., Kulikov A.V. 2015. The C1473G polymorphism in the tryptophan hydroxylase-2 gene: Involvement in ethanol-related behavior in mice. Neurosci. Lett.589, 79–82.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang X., Beaulieu J.M., Sotnikova T.D., Gainetdinov R.R., Caron M.G. 2004). Tryptophan hydroxylase-2 controls brain synthesis. Science.305, 217.

    Article  CAS  PubMed  Google Scholar 

  19. Kulikov A.V., Osipova D.V., Naumenko V.S., Popova N.K. 2005. Association between Tph2 gene polymorphism, brain tryptophan hydroxylase activity and aggressiveness in mouse strains. Genes Brain Behav.4, 482–485.

    Article  CAS  PubMed  Google Scholar 

  20. Walther D.J., Peter J.U., Bashammakh S., Hörtnagl H., Voits M., Fink H., Bader M. 2003. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science.299, 76.

    Article  CAS  PubMed  Google Scholar 

  21. Bazhenova E.Y., Fursenko D.V., Kulikova E.A., Khotskin N.V., Sinyakova N.A., Kulikov A.A. 2019. Effect of photoperiodic alterations on depression-like behavior and the brain serotonin system in mice genetically different in tryptophan hydroxylase 2 activity. Neurosci. Lett.699, 91‒96.

    Article  CAS  PubMed  Google Scholar 

  22. Otsuka T., Kawai M., Togo Y., Goda R., Kawase T., Matsuo H., Iwamoto A., Nagasawa M., Furuse M., Yasuo S. 2014. Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice. Psychoneuroendocrinology. 40, 37–47.

    Article  CAS  PubMed  Google Scholar 

  23. Goda R., Otsuka T., Iwamoto A., Kawai M., Shibata S., Furuse M., Yasuo S. 2015. Serotonin levels in the dorsal raphe nuclei of both chipmunks and mice are enhanced by long photoperiod, but brain dopamine level response to photoperiod is species-specific. Neurosci. Lett.593, 95‒100.

    Article  CAS  PubMed  Google Scholar 

  24. Khotskin N.V., Bazhenova E.Yu., Kulikova E.A., Sorokin I.E., Kulikov A.V. 2019. Effect of C1473G polymorphism in tryptophan hydroxylase-2 gene daylight length on the behavior of mice. Zh. Vyssh. Nerv. Deyat.im.I.P. Pavlova. 69, 85‒94.

    Google Scholar 

  25. Popova N.K., Kulikov A.V., Kondaurova E.M., Tsybko A.S., Kulikova E.A., Krasnov I.B., Shenkman B.S., Bazhenova E.Y., Sinyakova N.A., Naumenko V.S. 2015. Risk neurogenes for long-term spaceflight: Dopamine and serotonin brain system. Mol. Neurobiol. 51, 1443–1451.

    Article  CAS  PubMed  Google Scholar 

  26. Savelieva K.V., Zhao S., Pogorelov V.M., Rajan I., Yang Q., Cullinan E., Lanthorn T.H. 2008. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS One.3, 10.

    Article  CAS  Google Scholar 

  27. Alenina N., Kikic D., Todiras M., Mosienko V., Qadri F., Plehm R., Boyé P., Vilianovitch L., Sohr R., Tenner K., Hörtnagl H., Bader M. 2009. Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc. Natl. Acad. Sci. U. S. A.106, 10332‒10337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kovaenko I.L., Sagin D.A., Galyamina A.G., Orlov Yu.L., Kudryavtseva N.N. 2016. Changes in the expression of dopaminergic genes in brain structures of male mice exposed to chronic social defeat stress: An RNA-seq study. Mol. Biol. (Moscow). 50 (1), 161–163.

    Article  CAS  Google Scholar 

  29. Kudryavtseva N.N., Smagin D.A., Kovalenko I.L., Galyamina A.G., Vishnivetskaya G.B., Babenko V.N., Orlov Yu.L. 2017. Serotonergic genes in the development of anxiety/depression-like state and pathology of aggressive behavior in male mice: RNA-seq data. Mol. Biol. (Moscow). 51 (2), 251‒262.

    Article  CAS  Google Scholar 

  30. Galyamina A.G., Kovalenko I.L., Smagin D.A., Kudryavtseva N.N. 2017. Changes in the expression of neurotransmitter system genes in the ventral tegmental area of depressed mice: RNA-seq data. Zh. Vyssh. Nerv. Deyat.im.I.P. Pavlova.67, 113‒128.

    CAS  Google Scholar 

  31. Loseva E.V., Sarkisova K.Yu., Loginova N.A., Kudrin V.S. 2015. depressive behavior and monoamine contents in brain structure of rats during chronic overcrowding. Bull. Exp. Biol. Med.159 (3), 327‒330.

    Article  CAS  PubMed  Google Scholar 

  32. Sarkisova K.Yu., Kulikov M.A., Kudrin V.S., Narke-vich V.B., Midzyanovskaya I.S., Biryukova L.M., Folomkina A.A., Bazyan A.S. 2017. Neurochemical mechanisms of depression-like behavior in WAG/Rij rats. Zh. Vyssh. Nerv. Deyat.im.I.P. Pavlova.63 (3), 303‒315.

    Google Scholar 

  33. Loseva E.V., Loginova N.A., Sarkisova K.Yu., Klodt P.M., Narkevich V.B., Kudrin V.S. 2017. Behavioral symptoms of anxiety and depression and brain monoamine contents in rats after chronic intranasal administration of interferon-α. Ross. Fiziol. Zh. im. I.M. Sechenova.103, 417‒431.

    Google Scholar 

  34. Itzhacki J., Clesse D., Goumon Y., Van Someren E.J., Mendoza J. 2018. Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod. Brain Struct. Funct.223, 2641‒2652.

    Article  CAS  PubMed  Google Scholar 

  35. Lonstein J.S., Linning-Duffy K., Yan L. 2019. Low daytime light intensity disrupts male copulatory behavior and upregulates medial preoptic area steroid hormone and dopamine receptor expression in a diurnal rodent model of seasonal affective disorder. Front. Behav. Neurosci.13, 72‒83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Jackson C.R., Capozzi M., Dai H., McMahon D.G. 2014. Circadian perinatal photoperiod has enduring effects on retinal dopamine and visual function. J. Neurosci. 34, 4627‒4633.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Gutknecht L., Araragi N., Merker S., Waider J., Sommerlandt F.M., Mlinar B., Baccini G., Mayer U., Proft F., Hamon M., Schmitt A.G., Corradetti R., Lanfumey L., Lesch K.P. 2012. Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification. PLoS One. 2012. 7, e43157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Weng R., Shen S., Tian Y., Burton C., Xu X., Liu Y., Chang C., Bai Y., Liu H. 2015. Metabolomics approach reveals integrated metabolic network associated with serotonin deficiency. Sci. Rep. 5, 11864.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Dulcis D., Jamshidi P., Leutgeb S., Spitzer N.C. 2013. Neurotransmitter switching in the adult brain regulates behavior. Science.340, 449–453.

    Article  CAS  PubMed  Google Scholar 

  40. Young W., Cope Z.A., Romoli B., Schrurs E., Joosen A., Van Enkhuizen J., Sharp R.F., Dulcis D. 2018. Mice with reduced DAT levels recreate seasonal-induced switching between states in bipolar disorder. Neuropsychopharmacology.43, 1721–1731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ford C.P. 2014. The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience. 282, 13‒22.

    Article  CAS  PubMed  Google Scholar 

  42. Tsai H.Y., Chen K.C., Yang Y.K., Chen P.S., Yeh T.L., Chiu N.T., Lee I.H. 2011. Sunshine-exposure variation of human striatal dopamine D(2)/D(3) receptor availability in healthy volunteers. Prog. Neuropsychopharmacol. Biol. Psychiatry. 35, 107‒110.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Russian Foundation for Basic Research (project no. 17-04-00266). The breeding and keeping of animals was supported by the projects nos. 0259-2019-0002 and RFMEFI62117X0015.

Author information

Authors and Affiliations

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

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

Authors
  1. N. A. Sinyakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Yu. Bazhenova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Kulikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. V. Fursenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. V. Kulikov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. A. Sinyakova.

Ethics declarations

Conflict of Interests. The authors declare that they have no conflict of interest.

Statement of the Welfare of Animals. The keeping of animals and the experimental procedures complied with the rules of the Council of the European Parliament (Directive 2010/63/EU from September 22, 2010) and were approved by the Bioethics Committee of the Institute of Cytology and Genetics (Siberian Branch, Russian Academy of Sciences) (Protocol no. 16-01-007).

Additional information

Translated by A. Barkhash

Abbreviations: 5-HT, serotonin; DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; TPH2, tryptophan hydroxylase 2.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sinyakova, N.A., Bazhenova, E.Y., Kulikova, E.A. et al. Effect of the C1473G Polymorphic Variant of the Tryptophan Hydroxylase 2 Gene and Photoperiod Length on the Dopamine System of the Mouse Brain. Mol Biol 54, 51–58 (2020). https://doi.org/10.1134/S0026893320010148

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893320010148

Keywords:

Search

Navigation