TY  - JOUR
AU  - Vesković, Ana
AU  - Nakarada, Đura
AU  - Pavićević, Aleksandra
AU  - Prokić, Bogomir
AU  - Perović, Milka
AU  - Kanazir, Selma
AU  - Popović-Bijelić, Ana
AU  - Mojović, Miloš
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4221
AB  - BACKGROUND Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. However, numerous Aβ-targeting treatments have failed in clinical trials. This implies the need to shift the re- search focus from Aβ to other pathological features of the disease. OBJECTIVE The aim of this study was to examine the interplay between mitochondrial dysfunction, oxidative stress and blood-brain barrier (BBB) disruption in AD pathology, using a novel approach that involves the application of electron paramagnetic resonance (EPR) spectroscopy. METHOD In vivo and ex vivo EPR spectroscopy using two spin probes (aminoxyl radicals) exhibit- ing different cell-membrane and BBB permeability were employed to assess BBB integrity and brain tissue redox status in the 5xFAD mouse model of AD. In vivo spin probe reduction decay was analyzed using a two-compartment pharmacokinetic model. Furthermore, 15 K EPR spectros- copy was employed to investigate the brain metal content. RESULTS This study has revealed an altered brain redox state, BBB breakdown, as well as ROS-me- diated damage to mitochondrial iron-sulfur clusters, and up-regulation of MnSOD in the 5xFAD model. CONCLUSION The EPR spin probes were shown to be excellent in vivo reporters of the 5xFAD neu- ronal tissue redox state, as well as the BBB integrity, indicating the importance of in vivo EPR spec- troscopy application in preclinical studies of neurodegenerative diseases.
PB  - Bentham Science Publishers Ltd.
T2  - Current Alzheimer Research
T1  - In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.
IS  - 1
VL  - 18
DO  - 10.2174/1567205018666210324121156
SP  - 25
EP  - 34
ER  - 

@article{
author = "Vesković, Ana and Nakarada, Đura and Pavićević, Aleksandra and Prokić, Bogomir and Perović, Milka and Kanazir, Selma and Popović-Bijelić, Ana and Mojović, Miloš",
year = "2021",
abstract = "BACKGROUND Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. However, numerous Aβ-targeting treatments have failed in clinical trials. This implies the need to shift the re- search focus from Aβ to other pathological features of the disease. OBJECTIVE The aim of this study was to examine the interplay between mitochondrial dysfunction, oxidative stress and blood-brain barrier (BBB) disruption in AD pathology, using a novel approach that involves the application of electron paramagnetic resonance (EPR) spectroscopy. METHOD In vivo and ex vivo EPR spectroscopy using two spin probes (aminoxyl radicals) exhibit- ing different cell-membrane and BBB permeability were employed to assess BBB integrity and brain tissue redox status in the 5xFAD mouse model of AD. In vivo spin probe reduction decay was analyzed using a two-compartment pharmacokinetic model. Furthermore, 15 K EPR spectros- copy was employed to investigate the brain metal content. RESULTS This study has revealed an altered brain redox state, BBB breakdown, as well as ROS-me- diated damage to mitochondrial iron-sulfur clusters, and up-regulation of MnSOD in the 5xFAD model. CONCLUSION The EPR spin probes were shown to be excellent in vivo reporters of the 5xFAD neu- ronal tissue redox state, as well as the BBB integrity, indicating the importance of in vivo EPR spec- troscopy application in preclinical studies of neurodegenerative diseases.",
publisher = "Bentham Science Publishers Ltd.",
journal = "Current Alzheimer Research",
title = "In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.",
number = "1",
volume = "18",
doi = "10.2174/1567205018666210324121156",
pages = "25-34"
}

Vesković, A., Nakarada, Đ., Pavićević, A., Prokić, B., Perović, M., Kanazir, S., Popović-Bijelić, A.,& Mojović, M.. (2021). In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.. in Current Alzheimer Research
Bentham Science Publishers Ltd.., 18(1), 25-34.
https://doi.org/10.2174/1567205018666210324121156

Vesković A, Nakarada Đ, Pavićević A, Prokić B, Perović M, Kanazir S, Popović-Bijelić A, Mojović M. In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.. in Current Alzheimer Research. 2021;18(1):25-34.
doi:10.2174/1567205018666210324121156 .

Vesković, Ana, Nakarada, Đura, Pavićević, Aleksandra, Prokić, Bogomir, Perović, Milka, Kanazir, Selma, Popović-Bijelić, Ana, Mojović, Miloš, "In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease." in Current Alzheimer Research, 18, no. 1 (2021):25-34,
https://doi.org/10.2174/1567205018666210324121156 . .

TY  - CONF
AU  - Novaković, Lazar
AU  - Živković, Suzana
AU  - Popović-Bijelić, Ana
AU  - Mišić, Danijela
AU  - Mojović, Miloš
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6189
AB  - Electron paramagnetic resonance spectroscopy (EPR) was applied for in vivo detection of oxidative stress induced by high ionic strengths in Centaurium erythraea Rafn (Gentianaceae), a herbaceous perennial often found on saline soils. Shoots of C. erythraea were cultured in vitro for 4 weeks on solid 1/2 MS medium, or 1/2 MS medium supplemented with 200 mM NaCl to induce salt stress and thus stimulate the production of reactive oxygen species (ROS), which is a common response of plant cells subjected to various types of biotic or abiotic stresses. The reduction of a stable cell-permeable aminoxyl radical spin probe, Tempo, was measured to assess the oxidative status of the control and salt-treated samples. In both types of samples, the reduction of Tempo showed zero-order kinetics. After one hour, the control reduced only 9% of the initial amount of the spin probe, whereas the sample grown with 200 mM NaCl reduced it by 20%. This may indicate that the plants grown in the presence of 200 mM NaCl produced higher amounts of ROS which are able to reduce the aminoxyl radical. The obtained results indicate that EPR can be used as a method for in vivo evaluation of the redox state of plants under stress conditions, and could also be useful in determining the salt-stress tolerance of plants. Further
studies, including different salt concentrations, and plant species, have to be conducted to verify these findings.
PB  - Belgrade: Serbian Plant Physiology Society
C3  - Book of Abstracts: 2nd International Conference on Plant Biology, 21th Symposium of the Serbian Plant Physiology Society, and CОST Action FA1106 Quality Fruit Workshop; 2015 Jun 17-20; Petnica, Serbia
T1  - Application of Tempo EPR spin probe for in vivo detection of salt-induced oxidative stress in Centaurium erythraea Rafn
SP  - 178
EP  - 179
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6189
ER  - 

@conference{
author = "Novaković, Lazar and Živković, Suzana and Popović-Bijelić, Ana and Mišić, Danijela and Mojović, Miloš",
year = "2015",
abstract = "Electron paramagnetic resonance spectroscopy (EPR) was applied for in vivo detection of oxidative stress induced by high ionic strengths in Centaurium erythraea Rafn (Gentianaceae), a herbaceous perennial often found on saline soils. Shoots of C. erythraea were cultured in vitro for 4 weeks on solid 1/2 MS medium, or 1/2 MS medium supplemented with 200 mM NaCl to induce salt stress and thus stimulate the production of reactive oxygen species (ROS), which is a common response of plant cells subjected to various types of biotic or abiotic stresses. The reduction of a stable cell-permeable aminoxyl radical spin probe, Tempo, was measured to assess the oxidative status of the control and salt-treated samples. In both types of samples, the reduction of Tempo showed zero-order kinetics. After one hour, the control reduced only 9% of the initial amount of the spin probe, whereas the sample grown with 200 mM NaCl reduced it by 20%. This may indicate that the plants grown in the presence of 200 mM NaCl produced higher amounts of ROS which are able to reduce the aminoxyl radical. The obtained results indicate that EPR can be used as a method for in vivo evaluation of the redox state of plants under stress conditions, and could also be useful in determining the salt-stress tolerance of plants. Further
studies, including different salt concentrations, and plant species, have to be conducted to verify these findings.",
publisher = "Belgrade: Serbian Plant Physiology Society",
journal = "Book of Abstracts: 2nd International Conference on Plant Biology, 21th Symposium of the Serbian Plant Physiology Society, and CОST Action FA1106 Quality Fruit Workshop; 2015 Jun 17-20; Petnica, Serbia",
title = "Application of Tempo EPR spin probe for in vivo detection of salt-induced oxidative stress in Centaurium erythraea Rafn",
pages = "178-179",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6189"
}

Novaković, L., Živković, S., Popović-Bijelić, A., Mišić, D.,& Mojović, M.. (2015). Application of Tempo EPR spin probe for in vivo detection of salt-induced oxidative stress in Centaurium erythraea Rafn. in Book of Abstracts: 2nd International Conference on Plant Biology, 21th Symposium of the Serbian Plant Physiology Society, and CОST Action FA1106 Quality Fruit Workshop; 2015 Jun 17-20; Petnica, Serbia
Belgrade: Serbian Plant Physiology Society., 178-179.
https://hdl.handle.net/21.15107/rcub_ibiss_6189

Novaković L, Živković S, Popović-Bijelić A, Mišić D, Mojović M. Application of Tempo EPR spin probe for in vivo detection of salt-induced oxidative stress in Centaurium erythraea Rafn. in Book of Abstracts: 2nd International Conference on Plant Biology, 21th Symposium of the Serbian Plant Physiology Society, and CОST Action FA1106 Quality Fruit Workshop; 2015 Jun 17-20; Petnica, Serbia. 2015;:178-179.
https://hdl.handle.net/21.15107/rcub_ibiss_6189 .

Novaković, Lazar, Živković, Suzana, Popović-Bijelić, Ana, Mišić, Danijela, Mojović, Miloš, "Application of Tempo EPR spin probe for in vivo detection of salt-induced oxidative stress in Centaurium erythraea Rafn" in Book of Abstracts: 2nd International Conference on Plant Biology, 21th Symposium of the Serbian Plant Physiology Society, and CОST Action FA1106 Quality Fruit Workshop; 2015 Jun 17-20; Petnica, Serbia (2015):178-179,
https://hdl.handle.net/21.15107/rcub_ibiss_6189 .

TY  - CONF
AU  - Mandić-Kovačević, Nebojša
AU  - Živković, Suzana
AU  - Rakić, Tamara
AU  - Popović-Bijelić, Ana
PY  - 2014
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6393
AB  - The resurrection plant Ramonda serbica was completely dehydrated for 14 days, reaching 4.2 % of the relative water content, and then fully rehydrated for 24 h. During dehydration, the total phenolic and flavonoid contents of leaf extracts significantly increased, and then gradually decreased upon rehydration. These changes directly correspond to the observed antioxidant activity of extracts towards
the hydrophobic free radical DPPH. The scavenging potential towards the hydrophilic radical Tempone was maximal after 3 h of rehydration, indicating a strong oxidative burst upon water uptake.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2014. Vol. 1; 2014 Sep 22-26; Belgrade, Serbia
T1  - Antioxidant potential of the resurrection plant Ramonda serbica
SP  - 506
EP  - 509
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6393
ER  - 

@conference{
author = "Mandić-Kovačević, Nebojša and Živković, Suzana and Rakić, Tamara and Popović-Bijelić, Ana",
year = "2014",
abstract = "The resurrection plant Ramonda serbica was completely dehydrated for 14 days, reaching 4.2 % of the relative water content, and then fully rehydrated for 24 h. During dehydration, the total phenolic and flavonoid contents of leaf extracts significantly increased, and then gradually decreased upon rehydration. These changes directly correspond to the observed antioxidant activity of extracts towards
the hydrophobic free radical DPPH. The scavenging potential towards the hydrophilic radical Tempone was maximal after 3 h of rehydration, indicating a strong oxidative burst upon water uptake.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2014. Vol. 1; 2014 Sep 22-26; Belgrade, Serbia",
title = "Antioxidant potential of the resurrection plant Ramonda serbica",
pages = "506-509",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6393"
}

Mandić-Kovačević, N., Živković, S., Rakić, T.,& Popović-Bijelić, A.. (2014). Antioxidant potential of the resurrection plant Ramonda serbica. in Proceedings: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2014. Vol. 1; 2014 Sep 22-26; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 506-509.
https://hdl.handle.net/21.15107/rcub_ibiss_6393

Mandić-Kovačević N, Živković S, Rakić T, Popović-Bijelić A. Antioxidant potential of the resurrection plant Ramonda serbica. in Proceedings: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2014. Vol. 1; 2014 Sep 22-26; Belgrade, Serbia. 2014;:506-509.
https://hdl.handle.net/21.15107/rcub_ibiss_6393 .

Mandić-Kovačević, Nebojša, Živković, Suzana, Rakić, Tamara, Popović-Bijelić, Ana, "Antioxidant potential of the resurrection plant Ramonda serbica" in Proceedings: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2014. Vol. 1; 2014 Sep 22-26; Belgrade, Serbia (2014):506-509,
https://hdl.handle.net/21.15107/rcub_ibiss_6393 .