TY  - JOUR
AU  - Tasić, Danica
AU  - Opačić, Miloš
AU  - Kovačević, Sanja
AU  - Nikolić-Kokić, Aleksandra
AU  - Dimitrijević, Milena
AU  - Nikolić, Dušan
AU  - Vojnović-Milutinović, Danijela
AU  - Blagojević, Duško
AU  - Đorđević, Ana
AU  - Brkljačić, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5025
AB  - The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys
are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate
copper metabolism in a way that affects redox homeostasis, thus contributing to progression
of metabolic disturbances in the kidney. We determined protein level of copper transporters,
chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes
function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation
and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of
superoxide dismutase and decreased metallothionein level, while rendering the level of copper
importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi
network unaffected. Stress had no effect on renal copper metabolism. The activity and expression
of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose,
independently of stress, decreased renal copper level, and modulated renal copper metabolism
as to preserve vital cellular function including mitochondrial energy production and antioxidative
defense, at the expense of intracellular copper storage.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function
IS  - 16
VL  - 23
DO  - 10.3390/ijms23169023
SP  - 9023
ER  - 

@article{
author = "Tasić, Danica and Opačić, Miloš and Kovačević, Sanja and Nikolić-Kokić, Aleksandra and Dimitrijević, Milena and Nikolić, Dušan and Vojnović-Milutinović, Danijela and Blagojević, Duško and Đorđević, Ana and Brkljačić, Jelena",
year = "2022",
abstract = "The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys
are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate
copper metabolism in a way that affects redox homeostasis, thus contributing to progression
of metabolic disturbances in the kidney. We determined protein level of copper transporters,
chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes
function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation
and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of
superoxide dismutase and decreased metallothionein level, while rendering the level of copper
importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi
network unaffected. Stress had no effect on renal copper metabolism. The activity and expression
of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose,
independently of stress, decreased renal copper level, and modulated renal copper metabolism
as to preserve vital cellular function including mitochondrial energy production and antioxidative
defense, at the expense of intracellular copper storage.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function",
number = "16",
volume = "23",
doi = "10.3390/ijms23169023",
pages = "9023"
}

Tasić, D., Opačić, M., Kovačević, S., Nikolić-Kokić, A., Dimitrijević, M., Nikolić, D., Vojnović-Milutinović, D., Blagojević, D., Đorđević, A.,& Brkljačić, J.. (2022). Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function. in International Journal of Molecular Sciences
Basel: MDPI., 23(16), 9023.
https://doi.org/10.3390/ijms23169023

Tasić D, Opačić M, Kovačević S, Nikolić-Kokić A, Dimitrijević M, Nikolić D, Vojnović-Milutinović D, Blagojević D, Đorđević A, Brkljačić J. Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function. in International Journal of Molecular Sciences. 2022;23(16):9023.
doi:10.3390/ijms23169023 .

Tasić, Danica, Opačić, Miloš, Kovačević, Sanja, Nikolić-Kokić, Aleksandra, Dimitrijević, Milena, Nikolić, Dušan, Vojnović-Milutinović, Danijela, Blagojević, Duško, Đorđević, Ana, Brkljačić, Jelena, "Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function" in International Journal of Molecular Sciences, 23, no. 16 (2022):9023,
https://doi.org/10.3390/ijms23169023 . .

TY  - JOUR
AU  - Opačić, Miloš
AU  - Ristić, Aleksandar J.
AU  - Sokić, Dragoslav
AU  - Baščarević, Vladimir
AU  - Raičević, Savo
AU  - Savić, Slobodan
AU  - Zorović, Maja
AU  - Živin, Marko
AU  - Šelih, Vid Simon
AU  - Spasojević, Ivan
AU  - Savić, Danijela
PY  - 2021
UR  - https://onlinelibrary.wiley.com/doi/10.1002/brb3.1986
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4403
AB  - Introduction Disruption of copper homeostasis and dysfunction of mitochondria have been documented in sclerotic hippocampi (HS) of patients with mesial temporal lobe epilepsy (mTLE). However, a potential link between these pathological changes has not been tackled so far. Herein, we analyzed regional distribution of neuron somata density, copper concentration, and the activity of cytochrome c oxidase (CCO), a component of mitochondrial electron transport chain and copper-containing metalloprotein, in HS. Methods Histochemical staining and laser ablation inductively coupled plasma mass spectrometry were carried out to construct comparable maps of these parameters in coronal sections of hippocampi of 3 mTLE-HS patients and 3 control subjects. Results Copper levels were decreased in all regions of HS with pyramidal neuron somata. CCO activity was significantly reduced in stratum pyramidale (PY) 1 and cornu Ammonis field 4, the two regions with significant reduction in neuron somata density. CCO activity was also lower in layers that contain apical dendrites of pyramidal neurons and mossy fibers. It appears that copper deficiency in PY2 and PY3 comes before CCO activity reduction and neuronal loss. A strong positive correlation was found between neuron density, Cu concentration, and CCO activity. Conclusions Presented results imply that pathological alterations in Cu and energy metabolism could be involved in the development of HS. A limitation of this study was the relatively small number of patients. However, presented results underline copper deficiency as a component of pathological mechanisms of epilepsy and warrant further investigation of cuproproteins and members of copper transport machinery.
T2  - Brain and Behavior
T1  - Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients
IS  - 2
VL  - 11
DO  - 10.1002/brb3.1986
SP  - e01986
ER  - 

@article{
author = "Opačić, Miloš and Ristić, Aleksandar J. and Sokić, Dragoslav and Baščarević, Vladimir and Raičević, Savo and Savić, Slobodan and Zorović, Maja and Živin, Marko and Šelih, Vid Simon and Spasojević, Ivan and Savić, Danijela",
year = "2021",
abstract = "Introduction Disruption of copper homeostasis and dysfunction of mitochondria have been documented in sclerotic hippocampi (HS) of patients with mesial temporal lobe epilepsy (mTLE). However, a potential link between these pathological changes has not been tackled so far. Herein, we analyzed regional distribution of neuron somata density, copper concentration, and the activity of cytochrome c oxidase (CCO), a component of mitochondrial electron transport chain and copper-containing metalloprotein, in HS. Methods Histochemical staining and laser ablation inductively coupled plasma mass spectrometry were carried out to construct comparable maps of these parameters in coronal sections of hippocampi of 3 mTLE-HS patients and 3 control subjects. Results Copper levels were decreased in all regions of HS with pyramidal neuron somata. CCO activity was significantly reduced in stratum pyramidale (PY) 1 and cornu Ammonis field 4, the two regions with significant reduction in neuron somata density. CCO activity was also lower in layers that contain apical dendrites of pyramidal neurons and mossy fibers. It appears that copper deficiency in PY2 and PY3 comes before CCO activity reduction and neuronal loss. A strong positive correlation was found between neuron density, Cu concentration, and CCO activity. Conclusions Presented results imply that pathological alterations in Cu and energy metabolism could be involved in the development of HS. A limitation of this study was the relatively small number of patients. However, presented results underline copper deficiency as a component of pathological mechanisms of epilepsy and warrant further investigation of cuproproteins and members of copper transport machinery.",
journal = "Brain and Behavior",
title = "Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients",
number = "2",
volume = "11",
doi = "10.1002/brb3.1986",
pages = "e01986"
}

Opačić, M., Ristić, A. J., Sokić, D., Baščarević, V., Raičević, S., Savić, S., Zorović, M., Živin, M., Šelih, V. S., Spasojević, I.,& Savić, D.. (2021). Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients. in Brain and Behavior, 11(2), e01986.
https://doi.org/10.1002/brb3.1986

Opačić M, Ristić AJ, Sokić D, Baščarević V, Raičević S, Savić S, Zorović M, Živin M, Šelih VS, Spasojević I, Savić D. Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients. in Brain and Behavior. 2021;11(2):e01986.
doi:10.1002/brb3.1986 .

Opačić, Miloš, Ristić, Aleksandar J., Sokić, Dragoslav, Baščarević, Vladimir, Raičević, Savo, Savić, Slobodan, Zorović, Maja, Živin, Marko, Šelih, Vid Simon, Spasojević, Ivan, Savić, Danijela, "Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients" in Brain and Behavior, 11, no. 2 (2021):e01986,
https://doi.org/10.1002/brb3.1986 . .

TY  - JOUR
AU  - Korać Jačić, Jelena
AU  - Nikolić, Ljiljana
AU  - Stanković, Dalibor M.
AU  - Opačić, Miloš
AU  - Dimitrijević, Milena
AU  - Savić, Danijela
AU  - Grgurić Šipka, Sanja
AU  - Spasojević, Ivan
AU  - Bogdanović Pristov, Jelena
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3597
AB  - Upon release in response to stress, epinephrine (Epi) may interact with labile iron pool in human plasma with potentially important (patho)physiological consequences. We have shown that Epi and Fe3+ build stable 1:1 high-spin bidentate complex at physiological pH, and that Epi does not undergo degradation in the presence of iron. However, the interactions of Epi with the more soluble Fe2+, and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe2+ build colorless complex which is stable under anaerobic conditions. In the presence of O2, Epi promoted the oxidation of Fe2+ and the formation of Epi-Fe3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe2+ complex is very low (-582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe2+. Next, we examined the impact of iron binding on biological performance of Epi using patch clamping in cell culture with constitutive expression of adrenergic receptors. Epi alone evoked an increase of outward currents, whereas Epi in the complex with Fe3+ did not. This implies that the binding of Epi to adrenergic receptors and their activation is prevented by the formation of complex with iron. Pro-oxidative activity of Epi-Fe2+ complex may represent a link between chronic stress and cardiovascular problems. On the other hand, labile iron could serve as a modulator of biological activity of ligands. Such interactions may be important in human pathologies that are related to iron overload or deficiency.
T2  - Free Radical Biology and Medicine
T1  - Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.
VL  - 148
DO  - 10.1016/j.freeradbiomed.2020.01.001
SP  - 123
EP  - 127
ER  - 

@article{
author = "Korać Jačić, Jelena and Nikolić, Ljiljana and Stanković, Dalibor M. and Opačić, Miloš and Dimitrijević, Milena and Savić, Danijela and Grgurić Šipka, Sanja and Spasojević, Ivan and Bogdanović Pristov, Jelena",
year = "2020",
abstract = "Upon release in response to stress, epinephrine (Epi) may interact with labile iron pool in human plasma with potentially important (patho)physiological consequences. We have shown that Epi and Fe3+ build stable 1:1 high-spin bidentate complex at physiological pH, and that Epi does not undergo degradation in the presence of iron. However, the interactions of Epi with the more soluble Fe2+, and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe2+ build colorless complex which is stable under anaerobic conditions. In the presence of O2, Epi promoted the oxidation of Fe2+ and the formation of Epi-Fe3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe2+ complex is very low (-582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe2+. Next, we examined the impact of iron binding on biological performance of Epi using patch clamping in cell culture with constitutive expression of adrenergic receptors. Epi alone evoked an increase of outward currents, whereas Epi in the complex with Fe3+ did not. This implies that the binding of Epi to adrenergic receptors and their activation is prevented by the formation of complex with iron. Pro-oxidative activity of Epi-Fe2+ complex may represent a link between chronic stress and cardiovascular problems. On the other hand, labile iron could serve as a modulator of biological activity of ligands. Such interactions may be important in human pathologies that are related to iron overload or deficiency.",
journal = "Free Radical Biology and Medicine",
title = "Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.",
volume = "148",
doi = "10.1016/j.freeradbiomed.2020.01.001",
pages = "123-127"
}

Korać Jačić, J., Nikolić, L., Stanković, D. M., Opačić, M., Dimitrijević, M., Savić, D., Grgurić Šipka, S., Spasojević, I.,& Bogdanović Pristov, J.. (2020). Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.. in Free Radical Biology and Medicine, 148, 123-127.
https://doi.org/10.1016/j.freeradbiomed.2020.01.001

Korać Jačić J, Nikolić L, Stanković DM, Opačić M, Dimitrijević M, Savić D, Grgurić Šipka S, Spasojević I, Bogdanović Pristov J. Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.. in Free Radical Biology and Medicine. 2020;148:123-127.
doi:10.1016/j.freeradbiomed.2020.01.001 .

Korać Jačić, Jelena, Nikolić, Ljiljana, Stanković, Dalibor M., Opačić, Miloš, Dimitrijević, Milena, Savić, Danijela, Grgurić Šipka, Sanja, Spasojević, Ivan, Bogdanović Pristov, Jelena, "Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors." in Free Radical Biology and Medicine, 148 (2020):123-127,
https://doi.org/10.1016/j.freeradbiomed.2020.01.001 . .

TY  - CONF
AU  - Savić, Danijela
AU  - Opačić, Miloš
AU  - Brkljačić, Jelena
AU  - Ristić, Aleksandar
AU  - Sokić, Dragoslav
AU  - Baščarević, Vladimir
AU  - Raičević, Savo
AU  - Savić, Slobodan
AU  - Zorović, Maja
AU  - Živin, Marko
AU  - Šelih, Vid Simon
AU  - Spasić, Snežana
AU  - Spasojević, Ivan
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5882
AB  - More and more studies are identifying the regulation of metal homeostasis as one of the key points of central nervous system’s
well-being. Epilepsy is a particularly interesting neurological condition when viewed in terms of the correlation between the
amount of metals and the development of a seizure. This lecture will present contribution of our group to the field of metal
biology in epilepsy by mapping brain metals in sclerotic hippocampus resected from drug resistant mesial temporal lobe
epilepsy (mTLE) patients as surgical therapeutic approach. Direct insight into this epileptogenic area, by two powerful techniques,
optical emission and mass spectrometry, has led us to investigation of copper turnover. Namely, among the examined metals,
we found the deficiency of copper in sclerotic hippocampus on two levels: (i) in whole structure (ii) and locally in the areas of
neuronal loss, with significant correlation between copper concentration and neuron density. Furthermore, analysis of copper
metalloproteins showed: (i) significant increase or decrease in levels of protein that is participating in copper transport into
the cell (CTR1) depending on the degree of hippocampal neuronal loss; (ii) and lower activity of an enzyme in which copper
is part of the active site, cytochrome c oxidase, in sclerotic hippocampi of patients compared to control tissue. In our further
investigations it remained to be determined whether changes in copper concentrations and copper metalloproteins are causal
to pathology of mTLE or they represent epiphenomenon.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - The importance of copper in pathology of mesial temporal lobe epilepsy
SP  - 46
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5882
ER  - 

@conference{
author = "Savić, Danijela and Opačić, Miloš and Brkljačić, Jelena and Ristić, Aleksandar and Sokić, Dragoslav and Baščarević, Vladimir and Raičević, Savo and Savić, Slobodan and Zorović, Maja and Živin, Marko and Šelih, Vid Simon and Spasić, Snežana and Spasojević, Ivan",
year = "2019",
abstract = "More and more studies are identifying the regulation of metal homeostasis as one of the key points of central nervous system’s
well-being. Epilepsy is a particularly interesting neurological condition when viewed in terms of the correlation between the
amount of metals and the development of a seizure. This lecture will present contribution of our group to the field of metal
biology in epilepsy by mapping brain metals in sclerotic hippocampus resected from drug resistant mesial temporal lobe
epilepsy (mTLE) patients as surgical therapeutic approach. Direct insight into this epileptogenic area, by two powerful techniques,
optical emission and mass spectrometry, has led us to investigation of copper turnover. Namely, among the examined metals,
we found the deficiency of copper in sclerotic hippocampus on two levels: (i) in whole structure (ii) and locally in the areas of
neuronal loss, with significant correlation between copper concentration and neuron density. Furthermore, analysis of copper
metalloproteins showed: (i) significant increase or decrease in levels of protein that is participating in copper transport into
the cell (CTR1) depending on the degree of hippocampal neuronal loss; (ii) and lower activity of an enzyme in which copper
is part of the active site, cytochrome c oxidase, in sclerotic hippocampi of patients compared to control tissue. In our further
investigations it remained to be determined whether changes in copper concentrations and copper metalloproteins are causal
to pathology of mTLE or they represent epiphenomenon.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "The importance of copper in pathology of mesial temporal lobe epilepsy",
pages = "46",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5882"
}

Savić, D., Opačić, M., Brkljačić, J., Ristić, A., Sokić, D., Baščarević, V., Raičević, S., Savić, S., Zorović, M., Živin, M., Šelih, V. S., Spasić, S.,& Spasojević, I.. (2019). The importance of copper in pathology of mesial temporal lobe epilepsy. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 46.
https://hdl.handle.net/21.15107/rcub_ibiss_5882

Savić D, Opačić M, Brkljačić J, Ristić A, Sokić D, Baščarević V, Raičević S, Savić S, Zorović M, Živin M, Šelih VS, Spasić S, Spasojević I. The importance of copper in pathology of mesial temporal lobe epilepsy. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:46.
https://hdl.handle.net/21.15107/rcub_ibiss_5882 .

Savić, Danijela, Opačić, Miloš, Brkljačić, Jelena, Ristić, Aleksandar, Sokić, Dragoslav, Baščarević, Vladimir, Raičević, Savo, Savić, Slobodan, Zorović, Maja, Živin, Marko, Šelih, Vid Simon, Spasić, Snežana, Spasojević, Ivan, "The importance of copper in pathology of mesial temporal lobe epilepsy" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):46,
https://hdl.handle.net/21.15107/rcub_ibiss_5882 .

TY  - CONF
AU  - Opačić, Miloš
AU  - Zorović, Maja
AU  - Savić, Danijela
AU  - Živin, Marko
AU  - Raičević, Savo
AU  - Baščarević, Vladimir
AU  - Ristić, Aleksandar
AU  - Sokić, Dragoslav
AU  - Spasojević, Ivan
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5986
AB  - Aims: A drop in copper level and the loss of energy homeostasis are both portrayed in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) patients. Cytochrome c oxidase (COX) represents a crossroad of energy and copper metabolism; it is a key component of mitochondrial machinery and contains two copper centers. Our aim here was to examine the link between COX activity and the copper transporting system in HS. COX activity and the levels of mRNA of selected chaperones - COX11, COX17, Sco1 and Sco2 were determined in 13 anatomically distinct hippocampal regions. Methods: Study was performed on seven hippocampal samples, four of which had been acquired during the course of amygdalohippocampectomy treatment of medically intractable epilepsy and three control postmortem samples. Adjacent slices were used for Nissl staining, COX activity assay and mRNA in situ hybridization with autoradiography. Densitometry was performed using ImageJ. Results: Overall COX activity was decreased in HS compared to controls (P = 0.0003). However, 5 regions showed significantly lower COX activity in HS and 8 did not. Subiculum showed slightly higher activity in HS. The levels of mRNA levels were lowered in HS in 6 regions for COX11, 10 regions for COX17, two regions for Sco1 and 11 regions for Sco2. Conclusions: Our findings suggest the loss of energy homeostasis in HS may be related to pathological changes in specific components of copper delivery to COX, and that the impact may vary between different hippocampal regions.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Relationship Between Regional Distributions of Cytochrome C Oxidase and Copper-Delivering Chaperones in Sclerotic Hippocampi of Epilepsy Patients
SP  - 296
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5986
ER  - 

@conference{
author = "Opačić, Miloš and Zorović, Maja and Savić, Danijela and Živin, Marko and Raičević, Savo and Baščarević, Vladimir and Ristić, Aleksandar and Sokić, Dragoslav and Spasojević, Ivan",
year = "2019",
abstract = "Aims: A drop in copper level and the loss of energy homeostasis are both portrayed in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) patients. Cytochrome c oxidase (COX) represents a crossroad of energy and copper metabolism; it is a key component of mitochondrial machinery and contains two copper centers. Our aim here was to examine the link between COX activity and the copper transporting system in HS. COX activity and the levels of mRNA of selected chaperones - COX11, COX17, Sco1 and Sco2 were determined in 13 anatomically distinct hippocampal regions. Methods: Study was performed on seven hippocampal samples, four of which had been acquired during the course of amygdalohippocampectomy treatment of medically intractable epilepsy and three control postmortem samples. Adjacent slices were used for Nissl staining, COX activity assay and mRNA in situ hybridization with autoradiography. Densitometry was performed using ImageJ. Results: Overall COX activity was decreased in HS compared to controls (P = 0.0003). However, 5 regions showed significantly lower COX activity in HS and 8 did not. Subiculum showed slightly higher activity in HS. The levels of mRNA levels were lowered in HS in 6 regions for COX11, 10 regions for COX17, two regions for Sco1 and 11 regions for Sco2. Conclusions: Our findings suggest the loss of energy homeostasis in HS may be related to pathological changes in specific components of copper delivery to COX, and that the impact may vary between different hippocampal regions.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Relationship Between Regional Distributions of Cytochrome C Oxidase and Copper-Delivering Chaperones in Sclerotic Hippocampi of Epilepsy Patients",
pages = "296",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5986"
}

Opačić, M., Zorović, M., Savić, D., Živin, M., Raičević, S., Baščarević, V., Ristić, A., Sokić, D.,& Spasojević, I.. (2019). Relationship Between Regional Distributions of Cytochrome C Oxidase and Copper-Delivering Chaperones in Sclerotic Hippocampi of Epilepsy Patients. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 296.
https://hdl.handle.net/21.15107/rcub_ibiss_5986

Opačić M, Zorović M, Savić D, Živin M, Raičević S, Baščarević V, Ristić A, Sokić D, Spasojević I. Relationship Between Regional Distributions of Cytochrome C Oxidase and Copper-Delivering Chaperones in Sclerotic Hippocampi of Epilepsy Patients. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:296.
https://hdl.handle.net/21.15107/rcub_ibiss_5986 .

Opačić, Miloš, Zorović, Maja, Savić, Danijela, Živin, Marko, Raičević, Savo, Baščarević, Vladimir, Ristić, Aleksandar, Sokić, Dragoslav, Spasojević, Ivan, "Relationship Between Regional Distributions of Cytochrome C Oxidase and Copper-Delivering Chaperones in Sclerotic Hippocampi of Epilepsy Patients" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):296,
https://hdl.handle.net/21.15107/rcub_ibiss_5986 .

TY  - CONF
AU  - Savić, Danijela
AU  - Opačić, Miloš
AU  - Ristić, Aleksandar
AU  - Sokić, Dragoslav
AU  - Baščarević, Vladimir
AU  - Raičević, Savo
AU  - Savić, Slobodan
AU  - Živin, Marko
AU  - Šelih, Vid Simon
AU  - Spasić, Snežana
AU  - Spasojević, Ivan
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5887
AB  - The accumulating evidence on the relation between the disturbed metal homeostasis
and epilepsy urges the need for data regarding the total metal concentrations, as well
as metal distribution in the brain itself, in order to indicate where to direct the
potential therapy, to metal supplementation or chelation. This paper summarizes our
results on the measurements of some important essential metals in hippocampi of
patients with mesial temporal lobe epilepsy (mTLE) who underwent
amigdalohippocampectomy. The key findings point out that levels of copper and
manganese are deficient in hippocampi of mTLE patients, and that their
concentrations correlated positively with neuronal loss in affected regions of sclerotic
hippocampus. In addition, the Cu concentration was decreased in the areas of total
neuronal loss. Iron and zinc total hippocampal levels were neither accumulated nor
deficient compared to control. Our results contribute to deeper insight of metals
biology in the epilepsy and may represent the initial point of new and non-invasive
therapy of drug resistant epilepsy.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia
T1  - Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy
SP  - 105
EP  - 112
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5887
ER  - 

@conference{
author = "Savić, Danijela and Opačić, Miloš and Ristić, Aleksandar and Sokić, Dragoslav and Baščarević, Vladimir and Raičević, Savo and Savić, Slobodan and Živin, Marko and Šelih, Vid Simon and Spasić, Snežana and Spasojević, Ivan",
year = "2018",
abstract = "The accumulating evidence on the relation between the disturbed metal homeostasis
and epilepsy urges the need for data regarding the total metal concentrations, as well
as metal distribution in the brain itself, in order to indicate where to direct the
potential therapy, to metal supplementation or chelation. This paper summarizes our
results on the measurements of some important essential metals in hippocampi of
patients with mesial temporal lobe epilepsy (mTLE) who underwent
amigdalohippocampectomy. The key findings point out that levels of copper and
manganese are deficient in hippocampi of mTLE patients, and that their
concentrations correlated positively with neuronal loss in affected regions of sclerotic
hippocampus. In addition, the Cu concentration was decreased in the areas of total
neuronal loss. Iron and zinc total hippocampal levels were neither accumulated nor
deficient compared to control. Our results contribute to deeper insight of metals
biology in the epilepsy and may represent the initial point of new and non-invasive
therapy of drug resistant epilepsy.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia",
title = "Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy",
pages = "105-112",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5887"
}

Savić, D., Opačić, M., Ristić, A., Sokić, D., Baščarević, V., Raičević, S., Savić, S., Živin, M., Šelih, V. S., Spasić, S.,& Spasojević, I.. (2018). Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 105-112.
https://hdl.handle.net/21.15107/rcub_ibiss_5887

Savić D, Opačić M, Ristić A, Sokić D, Baščarević V, Raičević S, Savić S, Živin M, Šelih VS, Spasić S, Spasojević I. Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia. 2018;:105-112.
https://hdl.handle.net/21.15107/rcub_ibiss_5887 .

Savić, Danijela, Opačić, Miloš, Ristić, Aleksandar, Sokić, Dragoslav, Baščarević, Vladimir, Raičević, Savo, Savić, Slobodan, Živin, Marko, Šelih, Vid Simon, Spasić, Snežana, Spasojević, Ivan, "Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy" in Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia (2018):105-112,
https://hdl.handle.net/21.15107/rcub_ibiss_5887 .

TY  - JOUR
AU  - Opačić, Miloš
AU  - Stević, Zorica
AU  - Baščarević, Vladimir
AU  - Živić, Miroslav
AU  - Spasić, Mihajlo
AU  - Spasojević, Ivan
PY  - 2018
UR  - http://www.liebertpub.com/doi/10.1089/ars.2017.7433
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3065
AB  - The monitoring of progression in amyotrophic lateral sclerosis (ALS) relies on clinical outcome measures that take months to interpret, such as revised ALS functional rating scale (ALSFRS-R) score, with no approved biomarkers. A number of clinical studies have documented the involvement of oxidative stress in ALS pathology. Pertinent to this, we propose to evaluate oxidation-reduction potential (ORP) of cerebrospinal fluid (CSF) as a potential indicator of ALS progression. The case-control study included 24 patients with neurological non-neurodegenerative disorders (controls) and 82 ALS patients with different degrees of disease (ALSFRS-R score: 21-47). ORP was significantly higher in ALS patients than controls. It was not dependent on age or gender. A strong negative correlation was found between ORP and ALSFRS-R score for all patients and patients with spinal onset. In other words, ORP increased with ALS progression. No correlation was found for the subset of patients with bulbar onset, most likely because of the physical distance between neurodegenerative loci and the site of CSF collection. These results lead to the hypothesis that ORP of CSF has a potential as monitoring biomarker in ALS, particularly in the cohort of patients with spinal onset. Antioxid. Redox Signal. 28, 1570-1575.
T2  - Antioxidants and Redox Signaling
T1  - Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?
IS  - 17
VL  - 28
DO  - 10.1089/ars.2017.7433
SP  - 1570
EP  - 1575
ER  - 

@article{
author = "Opačić, Miloš and Stević, Zorica and Baščarević, Vladimir and Živić, Miroslav and Spasić, Mihajlo and Spasojević, Ivan",
year = "2018",
abstract = "The monitoring of progression in amyotrophic lateral sclerosis (ALS) relies on clinical outcome measures that take months to interpret, such as revised ALS functional rating scale (ALSFRS-R) score, with no approved biomarkers. A number of clinical studies have documented the involvement of oxidative stress in ALS pathology. Pertinent to this, we propose to evaluate oxidation-reduction potential (ORP) of cerebrospinal fluid (CSF) as a potential indicator of ALS progression. The case-control study included 24 patients with neurological non-neurodegenerative disorders (controls) and 82 ALS patients with different degrees of disease (ALSFRS-R score: 21-47). ORP was significantly higher in ALS patients than controls. It was not dependent on age or gender. A strong negative correlation was found between ORP and ALSFRS-R score for all patients and patients with spinal onset. In other words, ORP increased with ALS progression. No correlation was found for the subset of patients with bulbar onset, most likely because of the physical distance between neurodegenerative loci and the site of CSF collection. These results lead to the hypothesis that ORP of CSF has a potential as monitoring biomarker in ALS, particularly in the cohort of patients with spinal onset. Antioxid. Redox Signal. 28, 1570-1575.",
journal = "Antioxidants and Redox Signaling",
title = "Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?",
number = "17",
volume = "28",
doi = "10.1089/ars.2017.7433",
pages = "1570-1575"
}

Opačić, M., Stević, Z., Baščarević, V., Živić, M., Spasić, M.,& Spasojević, I.. (2018). Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?. in Antioxidants and Redox Signaling, 28(17), 1570-1575.
https://doi.org/10.1089/ars.2017.7433

Opačić M, Stević Z, Baščarević V, Živić M, Spasić M, Spasojević I. Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?. in Antioxidants and Redox Signaling. 2018;28(17):1570-1575.
doi:10.1089/ars.2017.7433 .

Opačić, Miloš, Stević, Zorica, Baščarević, Vladimir, Živić, Miroslav, Spasić, Mihajlo, Spasojević, Ivan, "Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?" in Antioxidants and Redox Signaling, 28, no. 17 (2018):1570-1575,
https://doi.org/10.1089/ars.2017.7433 . .

TY  - JOUR
AU  - Opačić, Miloš
AU  - Ristić, Aleksandar J
AU  - Savić, Danijela
AU  - Šelih, Vid Simon
AU  - Živin, Marko
AU  - Sokić, Dragoslav
AU  - Raičević, Savo
AU  - Baščarević, Vladimir
AU  - Spasojević, Ivan
PY  - 2017
UR  - http://xlink.rsc.org/?DOI=C6MT00293E
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28124054
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2583
AB  - The loss of metal homeostasis has been implicated in the pathophysiology of mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Here we applied laser ablation inductively coupled plasma mass spectrometry imaging to establish the spatial distribution of Zn, Fe, Cu and Mn in coronal sections of hippocampi of four patients with drug-resistant mTLE-HS who underwent amygdalohippocampectomy. Detailed maps of the metal concentrations in the different morphological areas/layers were built and analyzed. The highest level of Zn (>20 μg g(-1)) was found in mossy fiber-rich regions - cornu ammonis field 4 (CA4), gyrus dentatus, and CA3. The distribution of Fe appears to reflect the routes of the main intrahippocampal blood vessels. The highest concentrations of Cu (>10 μg g(-1)) and Mn (>15 μg g(-1)) were observed in regions/layers with neuron somata - subiculum, CA4, gyrus dentatus, and stratum pyramidale (SPy) in CA1 and CA2. Alveus and other regions with axons and dendrites generally showed lower levels of Zn, Cu, and Mn. The Cu concentration was decreased in the areas of total neuronal loss in SPy in CA1 (9.73 ± 0.91 μg g(-1)), compared to the subiculum (13.32 ± 1.29 μg g(-1); p = 0.043). The Cu and Mn concentrations correlated positively with neuron density in the SPy in CA1 (R = 0.629, p < 0.001; and R = 0.391, p = 0.004). These results provide a deeper insight into hippocampal metabolism of metals, and pave the road for identifying the components of the mechanism of epileptogenesis among Cu and Mn transporters and metalloproteins.
T2  - Metallomics : integrated biometal science
T1  - Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy.
IS  - 2
VL  - 9
DO  - 10.1039/c6mt00293e
SP  - 141
EP  - 148
ER  - 

@article{
author = "Opačić, Miloš and Ristić, Aleksandar J and Savić, Danijela and Šelih, Vid Simon and Živin, Marko and Sokić, Dragoslav and Raičević, Savo and Baščarević, Vladimir and Spasojević, Ivan",
year = "2017",
abstract = "The loss of metal homeostasis has been implicated in the pathophysiology of mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Here we applied laser ablation inductively coupled plasma mass spectrometry imaging to establish the spatial distribution of Zn, Fe, Cu and Mn in coronal sections of hippocampi of four patients with drug-resistant mTLE-HS who underwent amygdalohippocampectomy. Detailed maps of the metal concentrations in the different morphological areas/layers were built and analyzed. The highest level of Zn (>20 μg g(-1)) was found in mossy fiber-rich regions - cornu ammonis field 4 (CA4), gyrus dentatus, and CA3. The distribution of Fe appears to reflect the routes of the main intrahippocampal blood vessels. The highest concentrations of Cu (>10 μg g(-1)) and Mn (>15 μg g(-1)) were observed in regions/layers with neuron somata - subiculum, CA4, gyrus dentatus, and stratum pyramidale (SPy) in CA1 and CA2. Alveus and other regions with axons and dendrites generally showed lower levels of Zn, Cu, and Mn. The Cu concentration was decreased in the areas of total neuronal loss in SPy in CA1 (9.73 ± 0.91 μg g(-1)), compared to the subiculum (13.32 ± 1.29 μg g(-1); p = 0.043). The Cu and Mn concentrations correlated positively with neuron density in the SPy in CA1 (R = 0.629, p < 0.001; and R = 0.391, p = 0.004). These results provide a deeper insight into hippocampal metabolism of metals, and pave the road for identifying the components of the mechanism of epileptogenesis among Cu and Mn transporters and metalloproteins.",
journal = "Metallomics : integrated biometal science",
title = "Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy.",
number = "2",
volume = "9",
doi = "10.1039/c6mt00293e",
pages = "141-148"
}

Opačić, M., Ristić, A. J., Savić, D., Šelih, V. S., Živin, M., Sokić, D., Raičević, S., Baščarević, V.,& Spasojević, I.. (2017). Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy.. in Metallomics : integrated biometal science, 9(2), 141-148.
https://doi.org/10.1039/c6mt00293e

Opačić M, Ristić AJ, Savić D, Šelih VS, Živin M, Sokić D, Raičević S, Baščarević V, Spasojević I. Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy.. in Metallomics : integrated biometal science. 2017;9(2):141-148.
doi:10.1039/c6mt00293e .

Opačić, Miloš, Ristić, Aleksandar J, Savić, Danijela, Šelih, Vid Simon, Živin, Marko, Sokić, Dragoslav, Raičević, Savo, Baščarević, Vladimir, Spasojević, Ivan, "Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy." in Metallomics : integrated biometal science, 9, no. 2 (2017):141-148,
https://doi.org/10.1039/c6mt00293e . .