We studied the effect of the C1473G polymorphism in the Tph2 gene that reduces the activity of the tryptophan hydroxylase 2 in the brain on the severity of changes in motor activity (23 h after intraperitoneal administration of 0.8 mg/kg LPS or saline) and on the level of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the endings of 5-HT neurons in the cortex, hippocampus, and striatum (24 h after administration) of mature male mice of congenic lines B6-1473CC (high activity) and B6-1473GG (low activity). The state of the immune system in these structures was assessed by the expression of genes for proinflammatory cytokines IL-1β and TNF. LPS caused a decrease in motor and exploratory activities and increased the expression of the Il1b and Tnf genes in the studied brain structures in mice of both genotypes. LPS did not affect the level of 5-HT in any of the studied brain structures, but dramatically increased the level of 5-HIAA in these structures. The influence of the C1473G polymorphism on the intensity of the LPS-dependent increase in the level of 5-HIAA in the cortex and striatum was shown: in B6-1473CC mice this increase was more pronounced than in B6-1473GG mice. Demonstration of the influence of this polymorphism on the response of the 5-HT system after stimulation of the innate immunity is important for understanding of the role of tryptophan hydroxylase 2 in the mechanism of adaptation of the nervous system during infections and for predicting and reducing the risks of mental disorders.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Wu H, Denna TH, Storkersen JN, Gerriets VA. Beyond a neurotransmitter: The role of serotonin in inflammation and immunity. Pharmacol. Res. 2019;140:100-114. doi: https://doi.org/10.1016/j.phrs.2018.06.015
Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003;299:76. doi: https://doi.org/10.1126/science.1078197
Savelieva KV, Zhao S, Pogorelov VM, Rajan I, Yang Q, Cullinan E, Lanthorn TH. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS One. 2008;3(10):e3301. doi: https://doi.org/10.1371/journal.pone.0003301
Kulikov AV, Osipova DV, Naumenko VS, Terenina E, Mormède P, Popova NK. A pharmacological evidence of positive association between mouse intermale aggression and brain serotonin metabolism. Behav. Brain Res. 2012;233(1):113-119. doi: https://doi.org/10.1016/j.bbr.2012.04.031
Kulikov AV, Naumenko VS, Voronova IP, Tikhonova MA, Popova NK. Quantitative RT-PCR assay of 5-HT1A and 5-HT2A serotonin receptor mRNAs using genomic DNA as an external standard. J. Neurosci. Methods. 2005;141(1):97-101. doi: https://doi.org/10.1016/j.jneumeth.2004.06.005
Zhang X, Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science. 2004;305:217. doi: https://doi.org/10.1126/science.1097540.
Bazhenova EY, Fursenko DV, Kulikova EA, Khotskin NV, Sinyakova NA, Kulikov AA. Effect of photoperiodic alterations on depression-like behavior and the brain serotonin system in mice genetically different in tryptophan hydroxylase 2 activity. Neurosci. Lett. 2019;699:91-96. doi: https://doi.org/10.1016/j.neulet.2019.01.041
Siesser WB, Zhang X, Jacobsen JP, Sotnikova TD, Gainetdinov RR, Caron MG. Tryptophan hydroxylase 2 genotype determines brain serotonin synthesis but not tissue content in C57Bl/6 and BALB/c congenic mice. Neurosci. Lett. 2010;481(1):6-11. doi: https://doi.org/10.1016/j.neulet.2010.06.035
Frenois F, Moreau M, O’Connor J, Lawson M, Micon C, Lestage J, Kelley KW, Dantzer R, Castanon N. Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressivelike behavior. Psychoneuroendocrinology. 2007;32(5):516-531. doi: https://doi.org/10.1016/j.psyneuen.2007.03.005
Kulikov AV, Tikhonova MA, Kulikov VA. Automated measurement of spatial preference in the open field test with transmitted lighting. J. Neurosci. Methods. 2008; 170(2):345-351. doi: https://doi.org/10.1016/j.jneumeth.2008.01.024
Khotskin NV, Plyusnina AV, Kulikova EA, Bazhenova EY, Fursenko DV, Sorokin IE, Kolotygin I, Mormede P, Terenina EE, Shevelev OB, Kulikov AV. On association of the lethal yellow (AY) mutation in the agouti gene with the alterations in mouse brain and behavior. Behav. Brain Res. 2019;359:446-456. doi: https://doi.org/10.1016/j.bbr.2018.11.013
Bazhenova EY, Bazovkina DV, Kulikova EA, Fursenko DV, Khotskin NV, Lichman DV, Kulikov AV. C1473G polymorphism in mouse tryptophan hydroxylase-2 gene in the regulation of the reaction to emotional stress. Neurosci. Lett. 2017;640:105-110. doi: https://doi.org/10.1016/j.neulet.2017.01.010
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 174, No. 8, pp. 160-165, August, 2022
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Komleva, P.D., Bazhenova, E.Y., Khotskin, N.V. et al. C1473G Polymorphism in Tph2 Gene Affects Activation of Serotonin Metabolism in Mouse Brain 24 h after LPS Administration. Bull Exp Biol Med 174, 199–204 (2022). https://doi.org/10.1007/s10517-023-05673-w
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-023-05673-w