Stevanović, Ivana

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  • Stevanović, Ivana (5)

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Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease

Zeljković Jovanović, Milica; Stanojević, Jelena; Stevanović, Ivana; Stekić, Anđela; Bolland, Samuel J.; Jasnić, Nebojša; Ninković, Milica; Zarić Kontić, Marina; Ilić, Tihomir V.; Rodger, Jennifer; Nedeljković, Nadežda; Dragić, Milorad

(2023)

TY  - JOUR
AU  - Zeljković Jovanović, Milica
AU  - Stanojević, Jelena
AU  - Stevanović, Ivana
AU  - Stekić, Anđela
AU  - Bolland, Samuel J.
AU  - Jasnić, Nebojša
AU  - Ninković, Milica
AU  - Zarić Kontić, Marina
AU  - Ilić, Tihomir V.
AU  - Rodger, Jennifer
AU  - Nedeljković, Nadežda
AU  - Dragić, Milorad
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11099
AB  - Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as one of the potential candidates for PD therapy. Intermittent theta burst stimulation (iTBS), an excitatory protocol of rTMS, has been shown to be beneficial in several animal models of neurodegeneration, including PD. The aim of this study was to investigate the effects of prolonged iTBS on motor performance and behavior and the possible association with changes in the NMDAR subunit composition in the 6-hydroxydopamine (6-OHDA)-induced experimental model of PD. Two-month-old male Wistar rats were divided into four groups: controls, 6-OHDA rats, 6-OHDA + iTBS protocol (two times/day/three weeks) and the sham group. The therapeutic effect of iTBS was evaluated by examining motor coordination, balance, spontaneous forelimb use, exploratory behavior, anxiety-like, depressive/anhedonic-like behavior and short-term memory, histopathological changes and changes at the molecular level. We demonstrated the positive effects of iTBS at both motor and behavioral levels. In addition, the beneficial effects were reflected in reduced degeneration of dopaminergic neurons and a subsequent increase in the level of DA in the caudoputamen. Finally, iTBS altered protein expression and NMDAR subunit composition, suggesting a sustained effect. Applied early in the disease course, the iTBS protocol may be a promising candidate for early-stage PD therapy, affecting motor and nonmotor deficits. © 2023 by the authors.
T2  - Cells
T1  - Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease
VL  - 12
IS  - 11
DO  - 10.3390/cells12111525
ER  - 
@article{
author = "Zeljković Jovanović, Milica and Stanojević, Jelena and Stevanović, Ivana and Stekić, Anđela and Bolland, Samuel J. and Jasnić, Nebojša and Ninković, Milica and Zarić Kontić, Marina and Ilić, Tihomir V. and Rodger, Jennifer and Nedeljković, Nadežda and Dragić, Milorad",
year = "2023",
abstract = "Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as one of the potential candidates for PD therapy. Intermittent theta burst stimulation (iTBS), an excitatory protocol of rTMS, has been shown to be beneficial in several animal models of neurodegeneration, including PD. The aim of this study was to investigate the effects of prolonged iTBS on motor performance and behavior and the possible association with changes in the NMDAR subunit composition in the 6-hydroxydopamine (6-OHDA)-induced experimental model of PD. Two-month-old male Wistar rats were divided into four groups: controls, 6-OHDA rats, 6-OHDA + iTBS protocol (two times/day/three weeks) and the sham group. The therapeutic effect of iTBS was evaluated by examining motor coordination, balance, spontaneous forelimb use, exploratory behavior, anxiety-like, depressive/anhedonic-like behavior and short-term memory, histopathological changes and changes at the molecular level. We demonstrated the positive effects of iTBS at both motor and behavioral levels. In addition, the beneficial effects were reflected in reduced degeneration of dopaminergic neurons and a subsequent increase in the level of DA in the caudoputamen. Finally, iTBS altered protein expression and NMDAR subunit composition, suggesting a sustained effect. Applied early in the disease course, the iTBS protocol may be a promising candidate for early-stage PD therapy, affecting motor and nonmotor deficits. © 2023 by the authors.",
journal = "Cells",
title = "Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease",
volume = "12",
number = "11",
doi = "10.3390/cells12111525"
}
Zeljković Jovanović, M., Stanojević, J., Stevanović, I., Stekić, A., Bolland, S. J., Jasnić, N., Ninković, M., Zarić Kontić, M., Ilić, T. V., Rodger, J., Nedeljković, N.,& Dragić, M.. (2023). Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease. in Cells, 12(11).
https://doi.org/10.3390/cells12111525
Zeljković Jovanović M, Stanojević J, Stevanović I, Stekić A, Bolland SJ, Jasnić N, Ninković M, Zarić Kontić M, Ilić TV, Rodger J, Nedeljković N, Dragić M. Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease. in Cells. 2023;12(11).
doi:10.3390/cells12111525 .
Zeljković Jovanović, Milica, Stanojević, Jelena, Stevanović, Ivana, Stekić, Anđela, Bolland, Samuel J., Jasnić, Nebojša, Ninković, Milica, Zarić Kontić, Marina, Ilić, Tihomir V., Rodger, Jennifer, Nedeljković, Nadežda, Dragić, Milorad, "Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease" in Cells, 12, no. 11 (2023),
https://doi.org/10.3390/cells12111525 . .
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Moderate radioprotective role of zeolite in rats

Pavlović, Miloš; Đukić, Mirjana; Vojvodić, Danilo; Ninković, Milica; Stevanović, Ivana; Đurić, Ana; Stanojević, Boban

(2021)

TY  - JOUR
AU  - Pavlović, Miloš
AU  - Đukić, Mirjana
AU  - Vojvodić, Danilo
AU  - Ninković, Milica
AU  - Stevanović, Ivana
AU  - Đurić, Ana
AU  - Stanojević, Boban
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9915
AB  - Background/Aim. Exposure of living organisms to γ-radiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 and 10 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group – MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total super-oxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. GSH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy.
AB  - Uvod/Cilj. Izlaganje živih organizama gama zračenju rezultira hiperprodukcijom slobodnih radikala. Cilj istraživanja je bio da se ispita da li subakutna ishrana dopunjena sa 5% mikronizovanog zeolita (MZC) ispoljava radiozaštitnu ulogu na osnovu statusa oksidativnog stresa (OS) u mozgu i 8-hidroksiguanozina (8-OH-dG) u plazmi pacova izloženih pojedinačnim dozama jonizujućeg zračenja od 2 i 10 Gray (Gy). Metode. Wistar pacovi su bili na četvoronedeljnoj normalnoj ishrani ili ishrani obogaćenoj sa 5% MZC, posle čega su bili izloženi pojedinačnom jonizujućem zračenju od 2 Gy, odnosno 10 Gy. Grupe pacova bile su: a) grupa pacova na normalnoj ishrani (kontrolna grupa i grupe 2Gy i 10Gy); b) grupa pacova na ishrani obogaćenoj sa 5% MZC (kontrolna grupa – MZC i grupe MZC+2Gy i MZC+10Gy). Meren je malondialdehid (MDA), glutation (GSH) i aktivnost ukupne (tSOD) i mangan superoksid dizmutaze (MnSOD) u osetljivim strukturama mozga (cerebelum, hipokampus i cerebralni korteks), a 8-OH-dG u plazmi. Rezultati. Biomarker MDA je bio niži u MZC+2Gy i MZC+10Gy grupama, u odnosu na grupe 2Gy i 10Gy. Aktivnost ukupne SOD je bila viša u grupi MZC+10Gy, u odnosu na grupu 10Gy. Najviši nivo GSH bio je u grupi 10Gy. U pređenju sa kontrolnom grupom, 8-OH-dG je bio izuzetno viši u grupama ozračenim sa 10 Gy, bez obzira na dijetetski režim i niži u grupama MZC+2Gy i 2Gy. Zaključak. Pacovi koji su bili na režimu ishrane obogaćene sa 5% MZC bili su delimično zaštićeni od zračenja, shodno redukovanoj moždanoj aktivnosti SOD pri 2 Gy i sniženom nivou MDA pri izlaganju zračenju od 2 i 10 Gy.
T2  - Vojnosanitetski pregled
T1  - Moderate radioprotective role of zeolite in rats
T1  - Umerena radioprotektivna uloga zeolita kod pacova
VL  - 78
IS  - 7
SP  - 760
EP  - 768
DO  - 10.2298/VSP190702136P
ER  - 
@article{
author = "Pavlović, Miloš and Đukić, Mirjana and Vojvodić, Danilo and Ninković, Milica and Stevanović, Ivana and Đurić, Ana and Stanojević, Boban",
year = "2021",
abstract = "Background/Aim. Exposure of living organisms to γ-radiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 and 10 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group – MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total super-oxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. GSH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy., Uvod/Cilj. Izlaganje živih organizama gama zračenju rezultira hiperprodukcijom slobodnih radikala. Cilj istraživanja je bio da se ispita da li subakutna ishrana dopunjena sa 5% mikronizovanog zeolita (MZC) ispoljava radiozaštitnu ulogu na osnovu statusa oksidativnog stresa (OS) u mozgu i 8-hidroksiguanozina (8-OH-dG) u plazmi pacova izloženih pojedinačnim dozama jonizujućeg zračenja od 2 i 10 Gray (Gy). Metode. Wistar pacovi su bili na četvoronedeljnoj normalnoj ishrani ili ishrani obogaćenoj sa 5% MZC, posle čega su bili izloženi pojedinačnom jonizujućem zračenju od 2 Gy, odnosno 10 Gy. Grupe pacova bile su: a) grupa pacova na normalnoj ishrani (kontrolna grupa i grupe 2Gy i 10Gy); b) grupa pacova na ishrani obogaćenoj sa 5% MZC (kontrolna grupa – MZC i grupe MZC+2Gy i MZC+10Gy). Meren je malondialdehid (MDA), glutation (GSH) i aktivnost ukupne (tSOD) i mangan superoksid dizmutaze (MnSOD) u osetljivim strukturama mozga (cerebelum, hipokampus i cerebralni korteks), a 8-OH-dG u plazmi. Rezultati. Biomarker MDA je bio niži u MZC+2Gy i MZC+10Gy grupama, u odnosu na grupe 2Gy i 10Gy. Aktivnost ukupne SOD je bila viša u grupi MZC+10Gy, u odnosu na grupu 10Gy. Najviši nivo GSH bio je u grupi 10Gy. U pređenju sa kontrolnom grupom, 8-OH-dG je bio izuzetno viši u grupama ozračenim sa 10 Gy, bez obzira na dijetetski režim i niži u grupama MZC+2Gy i 2Gy. Zaključak. Pacovi koji su bili na režimu ishrane obogaćene sa 5% MZC bili su delimično zaštićeni od zračenja, shodno redukovanoj moždanoj aktivnosti SOD pri 2 Gy i sniženom nivou MDA pri izlaganju zračenju od 2 i 10 Gy.",
journal = "Vojnosanitetski pregled",
title = "Moderate radioprotective role of zeolite in rats, Umerena radioprotektivna uloga zeolita kod pacova",
volume = "78",
number = "7",
pages = "760-768",
doi = "10.2298/VSP190702136P"
}
Pavlović, M., Đukić, M., Vojvodić, D., Ninković, M., Stevanović, I., Đurić, A.,& Stanojević, B.. (2021). Moderate radioprotective role of zeolite in rats. in Vojnosanitetski pregled, 78(7), 760-768.
https://doi.org/10.2298/VSP190702136P
Pavlović M, Đukić M, Vojvodić D, Ninković M, Stevanović I, Đurić A, Stanojević B. Moderate radioprotective role of zeolite in rats. in Vojnosanitetski pregled. 2021;78(7):760-768.
doi:10.2298/VSP190702136P .
Pavlović, Miloš, Đukić, Mirjana, Vojvodić, Danilo, Ninković, Milica, Stevanović, Ivana, Đurić, Ana, Stanojević, Boban, "Moderate radioprotective role of zeolite in rats" in Vojnosanitetski pregled, 78, no. 7 (2021):760-768,
https://doi.org/10.2298/VSP190702136P . .

Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis

Dragić, Milorad; Zeljković, Milica; Stevanović, Ivana; Adžić, Marija; Stekić, Anđela; Mihajlović, Katarina; Grković, Ivana; Ilić, Nela; Ilić, Tihomir V.; Nedeljković, Nadežda; Ninković, Milica

(2021)

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zeljković, Milica
AU  - Stevanović, Ivana
AU  - Adžić, Marija
AU  - Stekić, Anđela
AU  - Mihajlović, Katarina
AU  - Grković, Ivana
AU  - Ilić, Nela
AU  - Ilić, Tihomir V.
AU  - Nedeljković, Nadežda
AU  - Ninković, Milica
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10082
AB  - Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A2AR on glial cells is observed. Finally, increased glial A1R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.
T2  - Brain Sciences
T2  - Brain Sciences
T1  - Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis
VL  - 11
IS  - 6
SP  - 736
DO  - 10.3390/brainsci11060736
ER  - 
@article{
author = "Dragić, Milorad and Zeljković, Milica and Stevanović, Ivana and Adžić, Marija and Stekić, Anđela and Mihajlović, Katarina and Grković, Ivana and Ilić, Nela and Ilić, Tihomir V. and Nedeljković, Nadežda and Ninković, Milica",
year = "2021",
abstract = "Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A2AR on glial cells is observed. Finally, increased glial A1R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.",
journal = "Brain Sciences, Brain Sciences",
title = "Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis",
volume = "11",
number = "6",
pages = "736",
doi = "10.3390/brainsci11060736"
}
Dragić, M., Zeljković, M., Stevanović, I., Adžić, M., Stekić, A., Mihajlović, K., Grković, I., Ilić, N., Ilić, T. V., Nedeljković, N.,& Ninković, M.. (2021). Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis. in Brain Sciences, 11(6), 736.
https://doi.org/10.3390/brainsci11060736
Dragić M, Zeljković M, Stevanović I, Adžić M, Stekić A, Mihajlović K, Grković I, Ilić N, Ilić TV, Nedeljković N, Ninković M. Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis. in Brain Sciences. 2021;11(6):736.
doi:10.3390/brainsci11060736 .
Dragić, Milorad, Zeljković, Milica, Stevanović, Ivana, Adžić, Marija, Stekić, Anđela, Mihajlović, Katarina, Grković, Ivana, Ilić, Nela, Ilić, Tihomir V., Nedeljković, Nadežda, Ninković, Milica, "Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis" in Brain Sciences, 11, no. 6 (2021):736,
https://doi.org/10.3390/brainsci11060736 . .
4
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Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro

Dragić, Milorad; Milićević, Katarina; Adžić, Marija; Stevanović, Ivana; Ninković, Milica; Grković, Ivana; Anđus, Pavle; Nedeljković, Nadežda

(2021)

TY  - JOUR
AU  - Dragić, Milorad
AU  - Milićević, Katarina
AU  - Adžić, Marija
AU  - Stevanović, Ivana
AU  - Ninković, Milica
AU  - Grković, Ivana
AU  - Anđus, Pavle
AU  - Nedeljković, Nadežda
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9174
AB  - Astrocytes are the first responders to noxious stimuli by undergoing cellular and functional transition referred as reactive gliosis. Every acute or chronic disorder is accompanied by reactive gliosis, which could be categorized as detrimental (A1) of beneficial (A2) for nervous tissue. Another signature of pathological astrocyte activation is disturbed Ca2+ homeostasis, a common denominator of neurodegenerative diseases. Deregulation of Ca+ signaling further contributes to production of pro-inflammatory cytokines and reactive oxygen species. Trimethyltin (TMT) intoxication is a widely used model of hippocampal degeneration, sharing behavioral and molecular hallmarks of Alzheimer’s disease (AD), thus representing a useful model of AD-like pathology. However, the role of astrocyte in the etiopathology of TMT-induced degeneration as well as in AD is not fully understood. In an effort to elucidate the role of astrocytes in such pathological processes, we examined in vitro effects of TMT on primary cortical astrocytes. The application of a range of TMT concentrations (5, 10, 50, and 100 μM) revealed changes in [Ca2+]i in a dose-dependent manner. Specifically, TMT-induced Ca2+ transients were due to L-type voltage-gated calcium channels (VGCC). Additionally, TMT induced mitochondrial depolarization independent of extracellular Ca2+ and disturbed antioxidative defense of astrocyte in several time points (4, 6, and 24 h) after 10 μM TMT intoxication, inducing oxidative and nitrosative stress. Chronic exposure (24 h) to 10 μM TMT induced strong upregulation of main pro-inflammatory factors, components of signaling pathways in astrocyte activation, A1 markers, and VGCC. Taken together, our results provide an insight into cellular and molecular events of astrocyte activation in chronic neuroinflammation. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
T2  - Molecular Neurobiology
T1  - Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro
VL  - 58
IS  - 4
SP  - 1792
EP  - 1805
DO  - 10.1007/s12035-020-02273-x
ER  - 
@article{
author = "Dragić, Milorad and Milićević, Katarina and Adžić, Marija and Stevanović, Ivana and Ninković, Milica and Grković, Ivana and Anđus, Pavle and Nedeljković, Nadežda",
year = "2021",
abstract = "Astrocytes are the first responders to noxious stimuli by undergoing cellular and functional transition referred as reactive gliosis. Every acute or chronic disorder is accompanied by reactive gliosis, which could be categorized as detrimental (A1) of beneficial (A2) for nervous tissue. Another signature of pathological astrocyte activation is disturbed Ca2+ homeostasis, a common denominator of neurodegenerative diseases. Deregulation of Ca+ signaling further contributes to production of pro-inflammatory cytokines and reactive oxygen species. Trimethyltin (TMT) intoxication is a widely used model of hippocampal degeneration, sharing behavioral and molecular hallmarks of Alzheimer’s disease (AD), thus representing a useful model of AD-like pathology. However, the role of astrocyte in the etiopathology of TMT-induced degeneration as well as in AD is not fully understood. In an effort to elucidate the role of astrocytes in such pathological processes, we examined in vitro effects of TMT on primary cortical astrocytes. The application of a range of TMT concentrations (5, 10, 50, and 100 μM) revealed changes in [Ca2+]i in a dose-dependent manner. Specifically, TMT-induced Ca2+ transients were due to L-type voltage-gated calcium channels (VGCC). Additionally, TMT induced mitochondrial depolarization independent of extracellular Ca2+ and disturbed antioxidative defense of astrocyte in several time points (4, 6, and 24 h) after 10 μM TMT intoxication, inducing oxidative and nitrosative stress. Chronic exposure (24 h) to 10 μM TMT induced strong upregulation of main pro-inflammatory factors, components of signaling pathways in astrocyte activation, A1 markers, and VGCC. Taken together, our results provide an insight into cellular and molecular events of astrocyte activation in chronic neuroinflammation. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.",
journal = "Molecular Neurobiology",
title = "Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro",
volume = "58",
number = "4",
pages = "1792-1805",
doi = "10.1007/s12035-020-02273-x"
}
Dragić, M., Milićević, K., Adžić, M., Stevanović, I., Ninković, M., Grković, I., Anđus, P.,& Nedeljković, N.. (2021). Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro. in Molecular Neurobiology, 58(4), 1792-1805.
https://doi.org/10.1007/s12035-020-02273-x
Dragić M, Milićević K, Adžić M, Stevanović I, Ninković M, Grković I, Anđus P, Nedeljković N. Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro. in Molecular Neurobiology. 2021;58(4):1792-1805.
doi:10.1007/s12035-020-02273-x .
Dragić, Milorad, Milićević, Katarina, Adžić, Marija, Stevanović, Ivana, Ninković, Milica, Grković, Ivana, Anđus, Pavle, Nedeljković, Nadežda, "Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro" in Molecular Neurobiology, 58, no. 4 (2021):1792-1805,
https://doi.org/10.1007/s12035-020-02273-x . .
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Zeolite pretreatment accomplishes partial brain radioprotective role by reducing iron and oxidative / nitrosative stress in rats

Stanojević, Boban; Đukić, Mirjana; Stevanović, Ivana; Ninković, Milica; Đurić, Ana; Gobeljić, Borko; Apostolović, Milan; Pantelić, Ana; Zebić, Goran; Todorović, Lidija; Bojić, Tijana; Savovski, Kiril

(2018)

TY  - JOUR
AU  - Stanojević, Boban
AU  - Đukić, Mirjana
AU  - Stevanović, Ivana
AU  - Ninković, Milica
AU  - Đurić, Ana
AU  - Gobeljić, Borko
AU  - Apostolović, Milan
AU  - Pantelić, Ana
AU  - Zebić, Goran
AU  - Todorović, Lidija
AU  - Bojić, Tijana
AU  - Savovski, Kiril
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8863
AB  - The aim of our study was to test the effect of subacutely applied micronized zeolite [micronized clinoptilolite (MZC)] on brain status of iron (Fe), reactive oxygen and nitrogen species (ROS, RNS), and radioprotective role against brain oxidative/nitrosative stress (OS/NS) initiated by single ionizing radiation of 2 or 10Gray (Gy). Wistar rats on normal (n=18) and 5% MZC supplemented diet (n=18), during 4 weeks, were internally subdivided into 3 subgroups (6 rats in each subgroup), with one of subgroup remaining as a control, and the other two subjected to single ionizing radiation of 2Gy or 10Gy. Thus, we had groups on normal diet: C – controls, 2Gy and 10Gy; and on 5% MZC supplemented diet: MZC, MZC+2Gy and MZC+10Gy. Concentrations of nitrates (a final RNS metabolite) and superoxide anion radical (O2 •-) (an initial ROS) were measured in homogenates of selective vulnerable brain regions (cerebellum, hippocampus and forebrain cortex), while Fe was determined in whole brain of rats. Results documented a significant drop of Fe in MZC and MZC+2Gy/10Gy groups; decrease of O2 •- and nitrate in MZC group; almost equal drop of O2 •- , in 2Gy and MZC+2Gy groups; and nitrate increase in 10Gy and MZC+10Gy groups. We confirmed that subacute MZC pretreatment contributes to partially accomplished brain radioprotective effect in rats exposed to single radiation dose of 2Gy and 10Gy, probably due to reduced OS/NS and Fe.
T2  - Hrana i ishrana
T1  - Zeolite pretreatment accomplishes partial brain radioprotective role by reducing iron and oxidative / nitrosative stress in rats
VL  - 59
IS  - 2
SP  - 26
EP  - 32
DO  - 10.5937/hraish1801026s
ER  - 
@article{
author = "Stanojević, Boban and Đukić, Mirjana and Stevanović, Ivana and Ninković, Milica and Đurić, Ana and Gobeljić, Borko and Apostolović, Milan and Pantelić, Ana and Zebić, Goran and Todorović, Lidija and Bojić, Tijana and Savovski, Kiril",
year = "2018",
abstract = "The aim of our study was to test the effect of subacutely applied micronized zeolite [micronized clinoptilolite (MZC)] on brain status of iron (Fe), reactive oxygen and nitrogen species (ROS, RNS), and radioprotective role against brain oxidative/nitrosative stress (OS/NS) initiated by single ionizing radiation of 2 or 10Gray (Gy). Wistar rats on normal (n=18) and 5% MZC supplemented diet (n=18), during 4 weeks, were internally subdivided into 3 subgroups (6 rats in each subgroup), with one of subgroup remaining as a control, and the other two subjected to single ionizing radiation of 2Gy or 10Gy. Thus, we had groups on normal diet: C – controls, 2Gy and 10Gy; and on 5% MZC supplemented diet: MZC, MZC+2Gy and MZC+10Gy. Concentrations of nitrates (a final RNS metabolite) and superoxide anion radical (O2 •-) (an initial ROS) were measured in homogenates of selective vulnerable brain regions (cerebellum, hippocampus and forebrain cortex), while Fe was determined in whole brain of rats. Results documented a significant drop of Fe in MZC and MZC+2Gy/10Gy groups; decrease of O2 •- and nitrate in MZC group; almost equal drop of O2 •- , in 2Gy and MZC+2Gy groups; and nitrate increase in 10Gy and MZC+10Gy groups. We confirmed that subacute MZC pretreatment contributes to partially accomplished brain radioprotective effect in rats exposed to single radiation dose of 2Gy and 10Gy, probably due to reduced OS/NS and Fe.",
journal = "Hrana i ishrana",
title = "Zeolite pretreatment accomplishes partial brain radioprotective role by reducing iron and oxidative / nitrosative stress in rats",
volume = "59",
number = "2",
pages = "26-32",
doi = "10.5937/hraish1801026s"
}
Stanojević, B., Đukić, M., Stevanović, I., Ninković, M., Đurić, A., Gobeljić, B., Apostolović, M., Pantelić, A., Zebić, G., Todorović, L., Bojić, T.,& Savovski, K.. (2018). Zeolite pretreatment accomplishes partial brain radioprotective role by reducing iron and oxidative / nitrosative stress in rats. in Hrana i ishrana, 59(2), 26-32.
https://doi.org/10.5937/hraish1801026s
Stanojević B, Đukić M, Stevanović I, Ninković M, Đurić A, Gobeljić B, Apostolović M, Pantelić A, Zebić G, Todorović L, Bojić T, Savovski K. Zeolite pretreatment accomplishes partial brain radioprotective role by reducing iron and oxidative / nitrosative stress in rats. in Hrana i ishrana. 2018;59(2):26-32.
doi:10.5937/hraish1801026s .
Stanojević, Boban, Đukić, Mirjana, Stevanović, Ivana, Ninković, Milica, Đurić, Ana, Gobeljić, Borko, Apostolović, Milan, Pantelić, Ana, Zebić, Goran, Todorović, Lidija, Bojić, Tijana, Savovski, Kiril, "Zeolite pretreatment accomplishes partial brain radioprotective role by reducing iron and oxidative / nitrosative stress in rats" in Hrana i ishrana, 59, no. 2 (2018):26-32,
https://doi.org/10.5937/hraish1801026s . .