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Bilateral Project of Slovenia-Serbia governments [06-00-118/2018-09/22]

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Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients

Opačić, Miloš; Ristic, Aleksandar J; Sokic, Dragoslav; Baščarević, Vladimir; Raicević, Savo; Savić, Slobodan; Zorović, Maja; Zivin, Marko; Selih, Vid Simon; Spasojević, Ivan; Savić, Danijela Z

(Wiley, Hoboken, 2021)

TY  - JOUR
AU  - Opačić, Miloš
AU  - Ristic, Aleksandar J
AU  - Sokic, Dragoslav
AU  - Baščarević, Vladimir
AU  - Raicević, Savo
AU  - Savić, Slobodan
AU  - Zorović, Maja
AU  - Zivin, Marko
AU  - Selih, Vid Simon
AU  - Spasojević, Ivan
AU  - Savić, Danijela Z
PY  - 2021
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1515
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.
PB  - Wiley, Hoboken
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
ER  - 
@article{
author = "Opačić, Miloš and Ristic, Aleksandar J and Sokic, Dragoslav and Baščarević, Vladimir and Raicević, Savo and Savić, Slobodan and Zorović, Maja and Zivin, Marko and Selih, Vid Simon and Spasojević, Ivan and Savić, Danijela Z",
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.",
publisher = "Wiley, Hoboken",
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"
}
Opačić, M., Ristic, A. J., Sokic, D., Baščarević, V., Raicević, S., Savić, S., Zorović, M., Zivin, M., Selih, V. S., Spasojević, I.,& Savić, D. Z.. (2021). Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients. in Brain and Behavior
Wiley, Hoboken., 11(2).
https://doi.org/10.1002/brb3.1986
Opačić M, Ristic AJ, Sokic D, Baščarević V, Raicević S, Savić S, Zorović M, Zivin M, Selih VS, Spasojević I, Savić DZ. Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients. in Brain and Behavior. 2021;11(2).
doi:10.1002/brb3.1986 .
Opačić, Miloš, Ristic, Aleksandar J, Sokic, Dragoslav, Baščarević, Vladimir, Raicević, Savo, Savić, Slobodan, Zorović, Maja, Zivin, Marko, Selih, Vid Simon, Spasojević, Ivan, Savić, Danijela Z, "Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients" in Brain and Behavior, 11, no. 2 (2021),
https://doi.org/10.1002/brb3.1986 . .
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