THE SYSTEM OF SEROTONIN METABOLISM IN THE BRAIN OF RATS IN THE DEVELOPMENT OF GLUTAMATEINDUCED OBESITY AND ITS CORRECTION WITH NANOCRYSTALLINE CERIUM DIOXIDE
М.М. Kondro1, B.М. Vervega1, Т.І. Halenova2, О.М. Savchuk2, М.Ya. Spivak3
- Danylo Halytsky Lviv National Medical University, Ukraine
- Educational and Scientific Centre «Institute of Biology and
Medicine» at Taras Shevchenco National University of Kyiv, Ukraine
- D. K. Zabolotny Institute of Microbiology and Virology
National Academy of Sciences of Ukraine, Ukraine
DOI: https://doi.org/10.15407/fz70.06.040
Abstract
One of the causes of obesity is the body’s energy imbalance.
The aim of our work was to investigate the serotonin system
in the brain tissue of rats with glutamate-induced obesity
and its correction with nanocrystalline cerium dioxide.
The research was conducted on 30 white rats, divided into
3 groups of 10 animals each: 1st − intact control, 2nd −
simulation of obesity by administration of monosodium
glutamate to neonatal animals, 3rd − correction of obesity
using nanocrystalline cerium dioxide against the background
of neonatal administration of monosodium glutamate. To
confirm the presence of obesity, at 4 months of age, rats were
weighed, naso-anal length was measured, and Lee’s index was
calculated. It was found that rats after neonatal administration
of monosodium glutamate developed obesity, and the content
of serotonin in the brain decreased by 72.9% compared to the
control. The content of tryptophan, a precursor in the synthesis
of serotonin, in rats with glutamate-induced obesity was 93.3%
lower compared to controls. Tryptophan hydroxylase activity
in the brain of rats with glutamate-induced obesity tended to
decrease, and tryptophan decarboxylase activity increased by
65.9% compared to the controls. The activity of monoamine
oxidase in the brain of rats after neonatal administration of
monosodium glutamate increased by 41.7% compared to the
control, which indicates enhanced degradation of serotonin.
Indoleamine-2,3-dehydrogenase activity in the brain of rats
with glutamate-induced obesity increased by 122.2%, this
evidences activation of the alternative kynurenine pathway of
tryptophan metabolism in the brain. This may also be one of
the reasons for the reduced serotonin content in the brains of
rats with glutamate-induced obesity. Periodic administration
of nanocrystalline cerium dioxide to rats after neonatal sodium
glutamate administration prevented obesity and led to an
increase in serotonin and tryptophan content in the brain by
171.6% and 72.7%, respectively, a decrease in tryptophan
decarboxylase activity by 15.1%, an increase in monoamine
oxidase activity by 60.7% and a decrease in indoleamine2,3-dihydrogenase activity by 17.7% compared to rats after
neonatal sodium glutamate administration. We conclude
that the serotonin system is involved in the development of
glutamate-induced obesity, and that periodic administration
of nanocrystalline cerium dioxide significantly improves
serotonin metabolism parameters.
Keywords:
monosodium glutamate; obesity; brain; serotonin; nanocrystalline cerium dioxide
References
- Urbanovych AM, Laniush FV. The role of ghrelin and serotonin in the control of eating behavior in patients with obesity and diabetes mellitus type 2. Mìžnarod Endokrinol Žurn. 2020; 16(2): 145-51. [Ukrainian].
CrossRef
- Van Galen KA, Horst KW, Serlie MJ. Serotonin, food intake, and obesity. Obes Rev. 2021 Jul; 22(7): e13210.
CrossRef
PubMed PubMedCentral
- Dоnоvаn M, Tеcоtt L. Sеrоtоnіn аnd thе rеgulаtіоn оf mаmmаlіаn еnеrgy bаlаncе. Frоnt Nеurоscі. 2013;7.
- Аcеbеs І, Sаrаcíbаr G, Еchеvаrríа E. Sеlеctіvе sеrоtоnіn rеuptаkе іnhіbіtоrs аltеr NPY іmmunоstаіnіng іn thе rаt hypоthаlаmus. Nеurоscі Rеs Cоmmun. 2002; 30(3):185-96.
CrossRef
- Zhоu L, Suttоn G, Rоchfоrd J. Sеrоtоnіn 2C rеcеptоr аgоnіsts іmprоvе typе 2 dіаbеtеs vіа mеlаnоcоrtіn-4 rеcеptоr sіgnаlіng pаthwаys. Cеll Mеtаb. 2007; 6(5):398-405.
CrossRef
PubMed PubMedCentral
- Zhаng Z, Lі L, Yаng M. Іncrеаsеd plаsmа lеvеls оf nеsfаtіn-1 іn pаtіеnts wіth nеwly dіаgnоsеd typе 2 dіаbеtеs mеllіtus. Еxp Clіn Еndоcrіnоl Dіаbеt. 2011; 120(02): 91-5.
CrossRef
PubMed
- Bеrglund Е, Lіu C, Sohn J. Sеrоtоnіn 2C rеcеptоrs іn prооpіоmеlаnоcоrtіn nеurоns rеgulаtе еnеrgy аnd glucоsе hоmеоstаsіs. J Clіn Іnvеstіgаt. 2013; 123(12):5061-70.
CrossRef
PubMed PubMedCentral
- Nоnоgаkі K, Оhbа Y, Sumіі M. Sеrоtоnіn systеms uprеglаtе thе еxprеssіоn оf hypоthаlаmіc NUCB2 vіа 5HT2C rеcеptоrs аnd іnducе аnоrеxіа vіа а lеptіnіndеpеndеnt pаthwаy іn mіcе. Bіоchеm Bіоphys Rеs Cоmmun. 2008; 372:186-90.
- Konopelnyuk VV, Karpovets TP, Kot LI, Ostapchenko LI. Biosynthesis of serotonin in the brain of rats under conditions of obesity induced by compatible consumption of high calorie diet and 10% fructose solution as a possible target. Int J Health Sci Res. 2015;5(8):496-506.
- Kobylіak N, Vіrсhernko O, Falalyeyeva T, Kondro M, Beregova T, Bodnar P, Shсherbakov O, Bubnov R, Сaprnda M, Devel D, Sabo J, Kruzlіak P, Rodrіgo L, Opatrіlova R, Spіvak M. Сerіum dіoxіde nanopartісles possess antі-іnflammatory propertіes іn the сondіtіons of the obesіty-assoсіated NAFLD іn rats. Bіomed Pharmaсother. 2017 Jun;90:608-14.
CrossRef
PubMed
- 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.
CrossRef
PubMed
- Nakanishi Y, Tsuneyama K, Fujimoto M, Salunga TL, Nomoto K, An J-L, Takano Y, Lizuka S, Nagata M, Suzuki W, Shimada T, Aburada M, Nakano M, Selmi C, Gershwin ME. Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia. J Autoimmun. 2008;30(1-2):42-50.
CrossRef
PubMed
- Kobyliak N, Falalyeyeva T, Virchenko O, Mykchalchyshyn G, Bodnar P, Spivak M, Yankovski D, Beregova T, Ostapchenko L. Comparative experimental investigation on the efficacy of mono- and multiprobiotic strains in non-alcoholic fatty liver disease prevention. BMC Gastroenterol. 2016;16:34.
CrossRef
PubMed PubMedCentral
- Gaitonde MK. A fluorimetric method for the determination of tryptophan in animal tissues. Biochem J. 1974 Jun;139(3):625-31.
CrossRef
PubMed PubMedCentral
- Maksimenko EG, Savchenko VN. The level of tryptophan and serotonin in the convulsive readiness conditions of cerebrum. Kharkov Natl V.N. Karazin Univ. Med. 2000;1(494):40-3. [Ukrainian].
- Wеіssbаch H, Wааlkеs TP, Udеnfrіеnd S. А sіmptіfіеd mеthоd fоr mеаsurіng sеrоtоnіn іn tіssuе; sіmultаnеоus аssаy оf bоth sеrоtоnіn аnd hіstаmіnе. J Bіоl Chеm. 1957; 230(2):865-71.
- Kuhn DM, О'Cаllаghаn JP, Juskеvіch J, Lovenberg W. Аctіvаtіоn оf brаіn tryptоphаn hydrоxylаsе by АTP-Mg2+: Dеpеndеncе оn cаlmоdulіn. Bіоchеmіctry. 1980;77:4688-91.
CrossRef
PubMed PubMedCentral
- Balakleyevsky AI. Colorimetric method for determining monoamine oxidase activity in blood serum. Lab work. 1976;3:151-2.
- Sаngwаn R, Mіshrа S, Kumаr S. Dіrеct fluоrоmеtry оf phаsе-еxtrаctеd tryptаmіnе-bаsеd fаst quаntіtаtіvе аssаy оf L-tryptоphаn dеcаrbоxylаsе frоm Cаthаrаnthus rоsеus lеаf. Аnаlyt Bіоchеm. 1998;255(1):39-46.
- 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.
- Kondro MM, Halenova TI, Kuznietsova MIu, Savchuk OM. Insulin receptor expression in subcellular fraction of muscular and adipose tissue as the factor of the tissue insulin resistance development in rats under conditions of the high-energy diet. Fiziol Zh. 2013;2(59):59-64. [Ukrainian].
CrossRef
PubMed
- Caineiro IB, Toscano AE, Lacerda DC, de Sa Barreto da Cuhna M, de Castro RM, Deiro TCB, Medeiros JM. L-tryptophan administration and increase in cerebral serotonin levels: Systematic review. Eur J Pharmacol. 2018 Oct;836:129-35.
CrossRef
PubMed
- Strac DS, Pivac N, Muck-Seler D. The serotonergic system and cognitive function. Transl Neurosci. 2016;7:35-49.
CrossRef
PubMed PubMedCentral
- Karpovets TP. Involvement of the serotonin metabolism system in the mechanisms of development of obesity and insulin resistance [autoref.]. Kyiv Taras Shevchenko Natl Univ. 2015. [Ukrainian].
- Mezo-Gonzalez CE, Santillan JAG, Reyes-Castro, Gourdel M, Croyal M, Bolanos-Jimenez F. Obesityinduced memory deficits in female rats are oestrous cycle dependent and linked to impaired brain kynurenine pathway metabolism. Neuroendocrinology. 2023;113(5):549-62.
CrossRef
PubMed
- 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.
CrossRef
PubMed PubMedCentral
- Ahmed B, Sultana R, Greene MW. Adipose tissue and insulin resistance in obese. Biomed Pharmacother. 2021 May; 137: 111315.
CrossRef
PubMed
- Mirabelli M, Chiefari E, Arcidiacono B, Corigliano DM, Brunetti FSB, Maggisano V, Russo D, Foti DP, Brunetti A. Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases. Nutrients. 2020 Apr;12(4):1066.
CrossRef
PubMed PubMedCentral
- Caputo F, Mameli M, Sienkiewicz A, Licoccia S, Stellacci F, Ghibelli L, Traversa E. A novel synthetic approach of cerium oxide nanoparticles with improved biomedical activity. Sci Rep. 2017;7(1):4636.
CrossRef
PubMed PubMedCentral
- Moridi H, Hosseini SA, Shateri H, Kheiripour N, Kaki A, Hatami M, Ranjbar A. Protective effect of cerium oxide nanoparticle on sperm quality and oxidative damage in malathion-induced testicular toxicity in rats: An experimental study. Int J Reprod Biomed (Yazd). 2018;16(4):261-66.
CrossRef
- Louro H, Saruga A, Santos J, Pinhão M, Silva MJ. Biological impact of metal nanomaterials in relation to their physicochemical characteristics. Toxicol In Vitro. 2019;56:172-83.
CrossRef
PubMed
- Kondro M. Modulation of immune system parameters during the development of glutamate-induced steatohepatosis and its correction with multiprobiotic «Symbiter acidophilic» concentrated. Exp Clin Physiol Biochem. 2021,92(1):16-28.
CrossRef
|