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  - 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 .