Uticaj galektina-3 u modulaciji ponašanja
The role of galectin-3 in the modulation of behavior
Докторанд
Stajić, Dalibor D.Ментор
Lukić, Miodrag L.Чланови комисије
Rosić, GvozdenIlić, Tihomir V.
Lečić-Toševski, Dušica
Đonović, Nela
Метаподаци
Приказ свих података о дисертацијиСажетак
SAŽETAK:
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.
ABSTRACT:
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.
Факултет:
Универзитет у Крагујевцу, Факултет медицинских наукаДатум одбране:
20-12-2019Пројекти:
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