Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients
2021
Аутори
Opačić, MilošRistic, Aleksandar J
Sokic, Dragoslav
Baščarević, Vladimir
Raicević, Savo
Savić, Slobodan
Zorović, Maja
Zivin, Marko
Selih, Vid Simon
Spasojević, Ivan
Savić, Danijela Z
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 densit...y. 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.
Кључне речи:
temporal lobe epilepsy / MS / LA‐ / ICP‐ / hippocampal sclerosis / cytochrome c oxidase / copperИзвор:
Brain and Behavior, 2021, 11, 2Издавач:
- Wiley, Hoboken
Финансирање / пројекти:
- Bilateral Project of Slovenia-Serbia governments [06-00-118/2018-09/22]
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200053 (Универзитет у Београду, Институт за мултидисциплинарна истраживања) (RS-MESTD-inst-2020-200053)
DOI: 10.1002/brb3.1986
ISSN: 2162-3279
WoS: 000596917400001
Scopus: 2-s2.0-85097242323
Институција/група
Institut za multidisciplinarna istraživanjaTY - 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 . .