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 . .