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The role of galectin-3 in the modulation of behavior

dc.contributor.advisorLukić, Miodrag L.
dc.contributor.otherRosić, Gvozden
dc.contributor.otherIlić, Tihomir V.
dc.contributor.otherLečić-Toševski, Dušica
dc.contributor.otherĐonović, Nela
dc.creatorStajić, Dalibor D.
dc.date.accessioned2020-02-26T15:44:50Z
dc.date.available2020-02-26T15:44:50Z
dc.date.available2020-07-03T15:17:12Z
dc.date.issued2019-12-20
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/12010
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=7184
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1219/bdef:Content/download
dc.description.abstractSAŽETAK: Uvod: Galektin-3 (Gal-3) ima značajnu ulogu u brojnim biološkim i patološkim procesima, a posebno je bitan u sazrevanju i funkcionisanju nervnog sistema i nastanku neuroinflamacije. Glavni cilj ovog istraživanja bio je ispitivanje uticaja delecije gena za Gal-3 na ponašanje kod miševa soja C57/BL6. Materijal i metode: Razlike u ponašanju su evaluirane bihevioralnim testovima koji su sprovedeni kod WT (wild-type) i Gal-3-/- (engl. knockout, KO) C57BL/6 miševa, mužjaka, starosti 20 nedelja, u bazalnim uslovima, kao i 24 sata nakon intraperitonealne aplikacije lipopolisaharida (engl. lipopolysaccharide, LPS) (u jednoj dozi, 5 mg/kg). Odmah nakon toga, životinje su žrtvovane i određivani su nivoi ekspresije gena za moždani neurotrofni faktor (engl. brain-derived neurotrophic factor, BDNF), GABA-A receptorske subjedinice i proinflamacijske citokine, IL-6 (engl. interleukin-6) i TNF-α (engl. tumor necrosis factor-α) u mozgu (hipokampusu). Rezultati: Delecija gena za Gal-3 je u bazalnim uslovima imala izražen anksiogeni efekat. Ovaj efekat je bio udružen sa smanjenjem ekspresije gena i sadržaja IL-6 i TNF-α u hipokampusu. Deficijencija Gal-3 je bila praćena i smanjenjem genske ekspresije i BDNF-imunoreaktivnosti, posebno u CA1 hipokampalnom regionu. Takođe, delecija gena za Gal-3 je izazvala smanjenje ekspresije gena za subjedinice 2 i 5 GABA-A receptora u hipokampusu. Delecija gena za Gal-3 nije pokazala prodepresantni efekat u bazalnim uslovima. Anksiogeni efekat neuroinflamacije indukovane LPS-om je kod WT miševa bio udružen sa povećanom ekspresijom gena za IL-6, TNF-α i TLR4 u hipokampusu, kao i redukcijom genske i imunohistohemijske ekspresije hipokampalnog BDNF-a, uz značajnu redukciju GABAAR2S u odnosu na vrednosti koje su detektovane u bazalnim uslovima. Međutim, deficijencija Gal-3 je sprečila povećanje IL-6 i smanjenje genske ekspresije i imunoreaktivnosti BDNF-a, kao i redukciju hipokampalnih GABA-AR2S i na taj način ublažila anksiogeni efekat akutne neuroinflamacije. Zaključak: Rezultati ovog istraživanja ukazuju na to da su naizgled suprotni efekti delecije gena za Gal-3 na nivo anksioznosti (anksiogeni efekat u bazalnim uslovima i anksiolitički efekat tokom akutne neuroinflamacije) povezani sa promenama ekspresije i sadržaja IL-6, TNF-a, TLR4, GABA-ARS i BDNF-a u hipokampusu.sr
dc.description.abstractABSTRACT: Intraduction: Galectin-3 (Gal-3) plays a significant role in various biological and pathological processes, and is particulary important in maturation and function of nervous system and in promotion of neuroinflammation. The principle aim of this study was to examine the effects of Gal-3 gene deletion on behavior in C57/BL6 mice strain. Material and Methods: Behavioral differences were evaluated by behavioral tests carried out on WT (wild-type) and Gal-3-/- (knockout, KO) C57BL/6 mice, males, aged 20 weeks, in basal conditions, and 24 hours after an intraperitoneal application of lipopolysaccharide (LPS) (in a single dose, 5 mg/kg). After that, animals were sacrificed and levels of gene expressions of brain-derived neurotrophic factor (BDNF), GABA-A receptor subunits and proinflammatory cytokines, IL-6 (interleukin-6) and TNF-α (tumor necrosis factor-α) in the brain (hippocampus) were evaluated. Results: Deletion of the Gal-3 gene had an anxiogenic effect in basal conditions. This effect was accompanied by decrease in the gene expression and content of IL-6 and TNF-α in hippocampus. Gal-3 deficiency was also accompanied by decreases in gene expression and BDNF-immunoreactivity, predominantly in the CA1 region of hippocampus. Besides, the deletion of the Gal-3 gene resulted in decrease of hippocampal gene expression of GABA-A receptor subunits 2 and 5. Deletion of the Gal-3 gene did not show a pro-depressant effect under basal conditions. In WT mice, the anxiogenic effect of neuroinflammation induced by LPS, was followed by increased hippocampal IL-6, TNF-α and TLR4 gene expression, as well as by decreased gene and immunohistochemical expression of BDNF in hippocampus, with a significant reduction in GABA-AR2S in comparison with the values obtained in basal condition. However, Gal-3 gene deletion prevented the increase in IL-6 and the reduction in BDNF gene expression and immunoreactivity, as well as the reduction of hippocampal GABA-AR2S, and therefore attenuated the anxiogenic effect of acute neuroinflammation. Conclusion: The results of this study show that the apparently opposite effects of Gal-3 deficiency on the level of anxiety (anxiogenic effect in basal conditions and anxiolytic effect during acute neuroinflammation) are associated with changes in the gene expression and content of IL-6, TNF-a, TLR4, GABA-ARS and BDNF in hippocampus.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175069/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175071/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectgalektin-3 deficijencija, inflamacija, TLR4, BDNF, GABA-A receptor, anksioznost, depresija, hipokampussr
dc.subjectgalectin-3 deficiency, neuroinflammation, TLR4, BDNF, GABA-A receptor, behavior, anxiety, depression, hippocampusen
dc.titleUticaj galektina-3 u modulaciji ponašanjasr
dc.title.alternativeThe role of galectin-3 in the modulation of behavioren
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/49166/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/49167/Dalibor_Stajic_Medicinski.pdf


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