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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2025; 71(6): 59-66

SEROTONIN METABOLISM SYSTEM IN THE BRAIN OF RATS WITH GLUTAMATE-INDUCED OBESITY ON THE BACKGROUND OF PERIODIC ADMINISTRATION OF A MULTIPROBIOTIC

M.M. Kondro1, T.I. Galenova2, O.M. Savchuk2, T.V. Beregova2

  1. DNPE “Danylo Halytsky Lviv National Medical University”, Ukraine
  2. Educational and Scientific Center “Institute of Biology and Medicine” of Taras Shevchenko National University of Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz71.06.059


Abstract

The role of serotonin as a regulator of systemic energy homeostasis has been proven; however, the functioning of the serotonin system in rat brain tissue under conditions of glutamate-induced obesity (GIO) has been poorly studied. Our work aimed to determine the content of serotonin and indicators of its metabolism in the brain tissue of rats with GIO and on a background of its correction with the multiprobiotic “Symbiter acidophilus” concentrated. The study was conducted on 30 white male rats, divided into 3 groups. The first group is the intact control. In the second and third groups, obesity was modeled by administering monosodium glutamate (MSG) to animals in the neonatal period. Rats in the third group were administered a multiprobiotic orally (2-week course administration for 3 months after one month of age). It was found that in rats with GIO, the content of serotonin in the brain tissue was lower compared to controls. At the same time, the content of tryptophan, a substrate for serotonin synthesis, was also reduced. Monoamine oxidase (MAO) activity in the brains of rats with GIO increased compared to controls. In the brains of rats with GIO, tryptophan hydroxylase activity did not undergo statistically significant changes against the background of a significant increase in tryptophan decarboxylase and indoleamine-2,3-dehydrogenase activities. In rats, after neonatal administration of MSG on a background of periodic administration of a multiprobiotic, serotonin and tryptophan levels in brain tissue increased compared with rats after neonatal administration of MSG without correction. At the same time, the tryptophan content remained much lower than this value in intact rats of the control group. Periodic administration of a multiprobiotic to rats that had been given MSG in the neonatal period resulted in a decrease in MAO activity. However, MAO activity did not decrease to levels of intact controls. In the group of rats that were administered MSG in the neonatal period, periodic administration of a multiprobiotic did not affect tryptophan hydroxylase and tryptophan decarboxylase activity in the brain compared to rats with GIO and restored indoleamine-2,3-dehydrogenase activity in the brain of rats with GIO to the level of intact controls. Therefore, if in rats with the development of GIO, activation of the alternative kynurenine pathway of tryptophan metabolism in the brain was observed, which could be one of the reasons for the reduced serotonin content in the brain of rats in this group, then in rats with GIO, against the background of periodic administration of a multiprobiotic, we observed the classical serotonin pathway of tryptophan metabolism in the brain.

Keywords: obesity; monosodium glutamate; serotonin; brain; multiprobiotic.

Full text: (PDF, in Ukrainian)

References

  1. Breton J, Galmiche M, Dechelotte P. Dysbiotic gut bacteria in obesity: An overview of the metabolic mechanisms and therapeutic perspectives of next-generation probiotics. Microorganisms. 2022 Feb;10(2):452. doi: 10.3390/ microorganisms10020452.
    2. CrossRef PubMed PubMedCentral
  2. Abenavoli L, Scarpellini E, Colica C, Boccuto L, Salehi B, Sharifi-Rad J, et al. Gut microbiota and obesity: a role for probiotics. Nutrients. 2019;11(11):2690.
    3. CrossRef PubMed PubMedCentral
  3. Crovesy L, Masterson D, Rosado EL. Profile of the gut microbiota of adults with obesity: a systematic review. Eur J Clin Nutr. 2020;74(9):1251-62.
    4. CrossRef PubMed
  4. Obayomi OV , Olaniran AF, Olawoyin DC, Falade OV , Osemwegie OO, Owa SO. Role of enteric dysbiosis in the development of central obesity: A review. Sci Afr. 2024 Jun;24:e02204. CrossRef e02204.
    5. CrossRef
  5. Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, Kotani H, Yamaoka S, Miyake K, Aoe S, Kamei Y, Ogawa Y. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acidinduced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Tromb Vasc Biol. 2007; 27:84-91.
    6. CrossRef PubMed
  6. Savcheniuk OA, Virchenko OV, Falalyeyeva TM, Beregova TV , Babenko LP, Lazarenko LM, Demchenko OM, Bubnov RV , Spivak MY . The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and poortunities for prevention. EPMA J. 2014; 5:2.
    7. CrossRef PubMed PubMedCentral
  7. Timmerman HM, Koning CI, Mulder R, Rombouts FM, Beynen AC. Monostrain, multistrain and multispecies probiotics-A comparison of functionality and efficacy. Int J Food Microbiol. 2004; 96:219-33.
    8. CrossRef PubMed
  8. Fakhfouri G, Rahimian R, Dyhrfjeld-Jhnsen J, Zirak MR, Beaulieu JM. 5-HT3 Receptor antagonists in neurologic and neuropsychiatric disorders: the iceberg still lies beneath the surface. Pharm Rev. 2019 Jul;71(3):383-412. doi: 10.1124/pr.118.015487.
    9. CrossRef PubMed
  9. Sanabria ER, Pereira MF, Dolnikoff MS, Andrade IS, Ferreira AT, Cavalheiro EA, Fernandes MJ. Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats. Brain Res Bull. 2002;59:47-51.
    10. CrossRef.1016/S0361-9230(02)00837-7 PubMed
  10. Maksimenko EG, Savchenko VN. The level of tryptophan and serotonin in the convulsive readiness conditions of cerebrum. Kharkov Natl VN Karazin Univ. Med. 2000;1(494):40-3. [Ukrainian].
  11. Ostapchenko LI, Mykhailyk IV . Biological membranes: methods for studying structure and functions. Textbook. М.М. Кондро, Т.І. Галенова, О.М. Савчук, Т.В. Берегова 66 Kyiv: Publishing and Printing Center «Kyiv University», 2006. [Ukrainian].
  12. Kudо Y , Boyd CAR, Sargent IL. Mоdulаtіоn оf іndоlеаmіnе 2,3-dіоxygеnаsе by іntеrfеrоn-γ іn humаn plаcеntаl chоrіоnіc vіllі. Mоl Humаn Rеprоd. 2000;6(4):369-74.
  13. lvarez-Arrao V , Martn-Pelez S. Effects of probiotics and synbiotics on weight loss in subjects with overweight or obesity: A systematic review. Nutrients. 2021 Oct;13(10):3627. doi: 10.3390/nu13103627.
    14. CrossRef PubMed PubMedCentral
  14. Tom-Castro XM, Rodriguez-Arrastia M, Cardona D, Rueda-Ruzafa L, Molina-Torres G, Roman P. Probiotics as a therapeutic strategy in obesity and overweight: a systematic review. Benef Microbes. 2021 Feb;12(1):5-15. doi: 10.3920/BM2020.0111.
    15. CrossRef PubMed
  15. Miranda RA, Agostinho AR, Trevenzoli IH, Barella LF, Franco CCS, Trombini AB, Malta A, Gravena C, Torrezan R, Mathias PCF, De Oliveira JC. Insulin oversecretion in MSG-obese rats is related to alterations in cholinergic muscarinic receptor subtypes in pancreatic islets. Cell Physiol Biochem. 2014; 33(4): 1075-86.
    16. CrossRef PubMed
  16. Аndré C, Dіnеl А, Fеrrеіrа G. Dіеt-іnducеd оbеsіty prоgrеssіvеly аltеrs cоgnіtіоn, аnxіеty-lіkе bеhаvіоr аnd lіpоpоlysаcchаrіdе-іnducеd dеprеssіvе-lіkе bеhаvіоr: fоcus оn brаіn іndоlеаmіnе 2,3-dіоxygеnаsе аctіvаtіоn. Brаіn Bеhаv Іmmun. 2014;41:10-21.
  17. Konopelniuk V , Falalyeyeva T, Tsyryuk O, Savchenko Yu, Kobyliak N, Prybytko I, et al. The effects of Z56822977 on biosynthesis of serotonin in the brain of rats in the conditions of MSG-induced obesity. Endokrynol Polska. 2018;69(5):536-44. doi: 10.5603/ep.2018.0058. [Polska].
    18. CrossRef PubMed
  18. Oxenkrug G, Navrotska V . Extension of life span by down-regulation of enzymes catalyzing tryptophan conversion into kynurenine: Possible implications for mechanisms of aging. Exp Biol Med (Maywood). 2023 Apr;248(7):573- 7. doi: 10.1177/15353702231179411.
    19. CrossRef PubMed PubMedCentral
  19. Oh C-M, Namkung J, Go Y , Shong KE, Kim K, Kim H, et al. Regulation of systemic energy homeostasis by serotonin in adipose tissues. Nat Commun. 2015 Apr;6:6794. doi: 10.1038/ncomms7794.
    20. CrossRef PubMed PubMedCentral
  20. Berglund ED, Liu C, Sohn J-W, Liu T, Kim MH, Lee CE, et al. Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis. J Clin Invest. 2013 Dec;123(12):5061-70. doi: 10.1172/ JCI70338.
    21. CrossRef PubMed PubMedCentral
  21. Murphy DL, Lesch K-P. Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci. 2008 Feb;9(2):85-96. doi: 10.1038/nrn2284.
    22. CrossRef PubMed
  22. Slyusar NА, Saltanova SD. Tryptophan metabolism: role in modulating the function of the «brain - gut axis.» Med Today Tomorrow. 2024;93(3):14-22. https://doi. org/10.35339/msz.2024.93.3. sls [Ukrainian].
    23. CrossRef
  23. Kostiuchenko O, Lushnikova I, Skibo G. The role of gut microbiota metabolites in the regeneration and protection of nervous tissue: a narrative review. Regen Med Rep. 2024 Sept;1(1):12-30.
    24. CrossRef
  24. Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut- brain communication. Nat Rev Gastroenterol Hepatol. 2019;16:461-78.
    25. CrossRef PubMed
  25. Kondro ММ, Vervega BМ, Halenova ТІ, Savchuk ОМ, Spivak МYa. The system of serotonin metabolism in the brain of rats in the development of glutamate-induced obesity and its correction with nanocrystalline cerium dioxide. Fiziol Zh. 2024;70(6):40-47.
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