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Материалы конференции / Conference proceeding
© MIKHAILOVA E. V. UDC 616.8-092
DOI: 10.20333/25000136-2022-2-115
Molecular pathways of serotoninergic neurons regulation in murine brain in metabolic syndrome of various etiologies
E. V. Mikhailova
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, Russian Federation
Abstract. Serotonin system participates in control of feeding behavior and energy balance jointly with hypothalamic neurohormonal systems. Tryptophan hydroxylase-2 (TPH2) is a key enzyme in serotonin biosynthesis in CNS. We compared TPH2 level in the hypothalamus and the midbrain and to evaluate neuroprotective mechanisms activated in metabolic syndrome. Key words: serotonin, serotonin system, hypothalamus, obesity, metabolic syndrome.
Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest associated with the publication of this article. Citation: Mikhailova EV. Molecular pathways of serotoninergic neurons regulation in murine brain in metabolic syndrome of various etiologies. Siberian Medical Review. 2022;(2):115. DOI: 10.20333/25000136-2022-2-115
Serotonin system participates in control of feeding behavior and energy balance jointly with hypothalamic neurohormonal systems. Tryptophan hydroxylase-2 (TPH2) is a key enzyme in serotonin biosynthesis in CNS [1]. Midbrain dorsal raphe nucleus (DRN) is a main serotonin source for the hypothalamus. The aim of the study: to compare TPH2 level in the hypothalamus and the mid-brain and to evaluate neuroprotective mechanisms activated in metabolic syndrome of various etiologies. Results: In C57Bl/6J mice, after 16 weeks keeping on a high-calorie diet, diet-induced obesity (DIO) developed [3], and decreased TPH2 level was detected immunohistochemi-cally in DRN neurons [2;4]. With real-time PCR in DIO was shown decreased TPH2 mRNA level in the midbrain (p<0.05) and no changes in the hypothalamus [3]. In mice with genetically determined melanocortine obesity any changes in TPH2 level in DRN neurons were not detected [2], but with high-performance liquid chromatography was shown increased level of serotonin in hypothalamus and detected increased TPH2 gene expression in the hypothalamus with real-time PCR [3]. It can indicate the existence of alternative serotonin biosynthesis sources. The data of double immunolabeling indicates the possibility of TPH2 expression in hypothalamic neurons, which can be aimed to increase brain serotonin level in metabolic syndrome [3]. In DIO decreased Akt1-kinase mRNA level revealed in the midbrain, but it was detected decreased level of immunopositive-Akt1 in serotonin DRN neurons and increased phospho(serine-473)Akt1 level, as well as increased level of phospho(serine-19)TPH2 (p<0.05) and increased level of the neurotrophic factor (BDNF) (p<0.05). Thus, in DIO activates compensatory mechanisms aimed to maintain the serotonergic neurons vitality and their functional activity. Conclusions: obesity of various etiology differ in compensatory mechanisms aimed to increase of serotonin level in the hypothalamus.
References
1. Carkaci-Salli N, Salli U, Kuntz-Melcavage KL, Pennock MM, Ozgen H, Tekin I, Freeman WM, Vrana KE. TPH2 in the ventral tegmental area of the male rat brain. Brain Research Bulletin. 2011;84 (6):376-380.
2. Mikhailova EV, Romanova IV, Derkach KV, Vish-nevskaya ON, Shpakov AO. The Effect of Diet-Induced and Melanocortin Obesity on Expression of Tryptophan Hydroxylase 2 in the Dorsal Raphe Nucleus and Ventral Tegmental Area in Mice. July 2019. Journal of Evolutionary Biochemistry and Physiology. 55(4):293-301 DOI: 10.1134/S0022093019040057]
3. Mikhailova EV, Sviridova DL, Romanova IV, Derkach KV, Shpakov AO. Effects of Diet-Induced and Melano-cortin Obesity on the Expression of Tryptophan Hydrox-ylase 2 in Midbrain and Hypothalamus Neurons in Mice. Neuroscience and Behavioral Physiology. 2021;51(5):666-672. DOI: 10.1007/s11055-021-01119-w
4. Romanova IV, Derkach KV, Mikhrina AL, Sukhov IB, Mikhailova EV, Shpakov AO. The leptin, dopamine and serotonin receptors in hypothalamic pomc-neurons of normal and obese rodents. Neurochemical Research. 2018;43 (4):821-837.
Author information
Elena V. Mikhailova, Junior Researcher, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; Address: 44, Toreza Pr., St. Petersburg, Russian Federation 194223; e-mail: elenamikhailova87@gmail.com
Received 24 February 2022 Revision Received 25 February 2022 Accepted 11 March 2022
Сибирское медицинское обозрение. 2022;(2):115
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