Alterations in the Level of mRNA of  Tph1 ,  Tph2  Genes, Tryptophan Hydroxylase Activity and Serotonin Metabolism in Mouse Brain 5 Days after Lipopolysaccharide Administration

D. V. Sherbakov; Щербаков Д. В.; A. B. Arefieva; Арефьева А. Б.; P. D. Komleva; Комлева П. Д.; A. E. Iz’urov; Изъюров А. Е.; N. V. Khotskin; Хоцкин Н. В.; D. V. Bazovkina; Базовкина Д. В.; A. V. Kulikov; Куликов А. В.

doi:10.31857/S0026898423020209

Alterations in the Level of mRNA of Tph1, Tph2 Genes, Tryptophan Hydroxylase Activity and Serotonin Metabolism in Mouse Brain 5 Days after Lipopolysaccharide Administration

作者: Sherbakov D.V.¹, Arefieva A.B.¹, Komleva P.D.¹, Iz’urov A.E.¹, Khotskin N.V.¹, Bazovkina D.V.¹, Kulikov A.V.¹
隶属关系:
1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences
期: 卷 57, 编号 2 (2023)
页面: 299-306
栏目: МОЛЕКУЛЯРНАЯ БИОЛОГИЯ КЛЕТКИ: ОТ РЕПАРАЦИИ ДНК ДО МЕТАБОЛОМИКИ
URL: https://journals.rcsi.science/0026-8984/article/view/138650
DOI: https://doi.org/10.31857/S0026898423020209
EDN: https://elibrary.ru/EEWKAW
ID: 138650

如何引用文章

全文:

开放存取

##reader.subscriptionAccessGranted##
受限制的访问

订阅存取

详细
作者简介
参考
补充文件
统计

详细

Tryptophan hydroxylases 1 and 2 (TPH1 and TPH2) play the key role in the synthesis of a neurotransmitter and hormone, serotonin (5-HT) in peripheral organs and in the brain, respectively. The main aim of the present study was to clarify the distribution of mRNA of Tph1 and Tph2 genes in brain structures in norm and after inflammation. The experiments were carried out on young (4 weeks old) males of C57BL/6 mice. The animals were divided into three groups: intact, control, injected ip with saline, and injected ip with 2 mg/kg of bacterial lipopolysaccharide (LPS). Markers of inflammation, spleen and thymus mass were assayed 5 days after the saline or LPS administration. In their frontal cortex, hippocampus, striatum, hypothalamus and midbrain the concentrations of 5-HT, its main metabolite, 5-hydroxyindole acetic acid (5-HIAA), and TPH activity were assayed in using HPLC, while Tph1 and Tph2 mRNA were quantified by quantitative real-time RT-PCR. Dramatic increase of spleen mass and decrease of thymus mass 5 days after LPS administration was shown. Significant increase of 5-HT and 5-HIAA levels in midbrain as well as decrease of 5-HIAA concentration and TPH activity in hypothalamus in mice treated with LPS and saline compared with intact animals was revealed. The highest concentration of Tph2 gene mRNA was observed in midbrain in 5-HT neuron bodies, while in this gene mRNA level was lower in 5-HT endings (cortex, hippocampus, striatum and hypothalamus). Trace amounts of Tph1 mRNA was revealed in all studied brain structures in mice of the three groups. Thus, Tph1 gene expression in the mouse brain is too low to significantly affect 5-HT synthesis in normal conditions and during inflammation.

关键词

mice, tryptophan hydroxylase 1 и 2, serotonin, lipopolysaccharide, brain

参考

Gaspar P., Lillesaar C. (2012) Probing the diversity of serotonin neurons. Philos. Trans. R Soc. Lond. B Biol. Sci. 367, 2382–2394.
Willner P., Scheel-Krüger J., Belzung C. (2013) The neurobiology of depression and antidepressant action. Neurosci. Biobehav. Rev. 37, 2331–2371.
Hamon M., Blier P. (2013) Monoamine neurocircuitry in depression and strategies for new treatments. Prog. Neuropsychopharmacol. Biol. Psychiatry. 45, 54–63.
Miller B.R., Hen R. (2015) The current state of the neurogenic theory of depression and anxiety. Curr. Opin. Neurobiol. 30, 51–58.
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.
Walther D.J., Bader M. (2003) A unique central tryptophan hydroxylase isoform. Biochem. Pharmacol. 66, 1673–1680.
Patel P.D., Pontrello C., Burke S. (2004) Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland. Biol. Psychiatry. 55, 428–433
Sakowski S.A., Geddes T.J., Thomas D.M., Levi E., Hatfield J.S., Kuhn D.M. (2006) Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies. Brain Res. 1085, 11–18.
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, e3301.
Megha K., Deshmukh P.S., Ravi A.K., Tripathi A.K., Abegaonkar M.P., Banerjee B.D. (2015) Effect of low-intensity microwave radiation on monoamine neurotransmitters and their key regulating enzymes in rat brain. Cell Biochem. Biophys. 73, 93–100.
Igarashi K., Kuchiiwa T., Kuchiiwa S., Iwai H., Tomita K., Sato T. (2021) Kamishoyosan (a Japanese traditional herbal formula), which effectively reduces the aggressive biting behavior of male and female mice, and potential regulation through increase of Tph1, Tph2, and Esr2 mRNA levels. Brain Res. 1768, 147580.
Browne C.A., O’Brien F.E., Connor T.J., Dinan T.G., Cryan J.F. (2012) Differential lipopolysaccharide-induced immune alterations in the hippocampus of two mouse strains: effects of stress. Neurosci. 6, 237–248.
Zill P., Büttner A., Eisenmenger W., Möller H.J., Ackenheil M., Bondy B. (2007) Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post-mortem study. J. Psychiatr. Res. 41, 168–173.
Zill P., Büttner A., Eisenmenger W., Müller J., Möller H.J., Bondy B. (2009) Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: a postmortem study in human brain. Neuroscience. 159, 1274–1282.
Sugden K., Tichopad A., Khan N., Craig I.W., D’Souza U.M. (2009) Genes within the serotonergic system are differentially expressed in human brain. BMC. Neurosci. 10, 50.
Сорокин И.Е., Евсюкова В.С., Куликов А.В. (2022) Влияние короткого светового дня на поведение и серотониновую систему головного мозга рыб вида Danio rerio. Бюлл. Эксп. Биол. Мед. 173, 279–284.
Kulikov A.V., Naumenko V.S., Voronova I.P., Tikhonova M.A., Popova N.K. (2005) Quantitative RT-PCR of 5-HT1A and 5-HT2A serotonin receptor mRNAs using genomic DNA as an standard. J. Neurosci. Meth. 141, 97–101.
Науменко В.С., Куликов А.В. (2006) Количественное определение экспрессии гена 5-НТ1А серотонинового рецептора в головном мозге. Молекуляр. биология. 40, 37–44.
Bazhenova E.Y., Bazovkina D.V., Kulikova E.A., Fursenko D.V., Khotskin N.V., Lichman D.V., Kulikov A.V. (2017) C1473G polymorphism in mouse tryptophan hydroxylase-2 gene in the regulation of the reaction to emotional stress. Neurosci. Lett. 640, 105–110.
Bonthuis P.J., Huang W.C., Stacher Hörndli C.N., Ferris E., Cheng T., Gregg C. (2015) Noncanonical genomic imprinting effects in offspring. Cell Rep. 12, 979–991.
Livak K.J., Schmittgen T.D: (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25, 402–408.
Evsiukova V.S., Kulikova E.A., Kulikov A.V. (2021) Age-related alterations in the behavior and serotonin-related gene mRNA levels in the brain of males and females of short-lived turquoise killifish (Nothobranchius furzeri). Biomolecules. 11, 1421.