TY  - CONF
AU  - Zeković, Janko
AU  - Vidičević Novaković, Sašenka
AU  - Tasić, Jelena
AU  - Stanojević, Željka
AU  - Milovanović, Andona
AU  - Tomonjić, Nina
AU  - Petričević, Saša
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Trajković, Vladimir
AU  - Isaković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5839
AB  - Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5839
ER  - 

@conference{
author = "Zeković, Janko and Vidičević Novaković, Sašenka and Tasić, Jelena and Stanojević, Željka and Milovanović, Andona and Tomonjić, Nina and Petričević, Saša and Zogović, Nevena and Tovilović-Kovačević, Gordana and Trajković, Vladimir and Isaković, Aleksandra",
year = "2023",
abstract = "Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5839"
}

Zeković, J., Vidičević Novaković, S., Tasić, J., Stanojević, Ž., Milovanović, A., Tomonjić, N., Petričević, S., Zogović, N., Tovilović-Kovačević, G., Trajković, V.,& Isaković, A.. (2023). Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839

Zeković J, Vidičević Novaković S, Tasić J, Stanojević Ž, Milovanović A, Tomonjić N, Petričević S, Zogović N, Tovilović-Kovačević G, Trajković V, Isaković A. Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

Zeković, Janko, Vidičević Novaković, Sašenka, Tasić, Jelena, Stanojević, Željka, Milovanović, Andona, Tomonjić, Nina, Petričević, Saša, Zogović, Nevena, Tovilović-Kovačević, Gordana, Trajković, Vladimir, Isaković, Aleksandra, "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):80,
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

TY  - CONF
AU  - Paunović, Verica
AU  - Kosić, Milica
AU  - Arsikin-Csordas, Katarina
AU  - Firestone, Raymond A
AU  - Ristić, Biljana
AU  - Mirčić, Aleksandar
AU  - Petričević, Saša
AU  - Bošnjak, Mihajlo
AU  - Zogović, Nevena
AU  - Mandić, Miloš
AU  - Bumbaširević, Vladimir
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2019
UR  - https://www.fens.org/news-activities/fens-and-societies-calendar/meeting-event/fens-regional-meeting-2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6355
AB  - During malignant transformation cells acquire changes in metabolism, signaling pathways as well as organelle content. The preferential use of aerobic glycolysis (Warburg effect), along with the increased number and volume of lysosomes can be viewed as glioma cells’ Achilles heels. In the present study, we aimed to examine the in vitro antiglioma effects of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-D-glucose (2DG).
NDI-triggered LMP and 2DG-mediated glycolysis block synergistically induced rapid ATP depletion, mitochondrial damage, and reactive oxygen species (ROS) production causing necrotic cell death of U251 glioma cells, but not primary astrocytes. Lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol partially prevented NDI/2DG-induced glioma cell death, thus implying the involvement of LMP and oxidative stress in the observed cytotoxicity. Likewise, LMP-inducing agent chloroquine
showed synergistic cytotoxic effect with 2DG. Similarly, glucose deprivation as well as other glycolytic inhibitors, iodoacetate and sodium fluoride, synergistically cooperated with NDI, further corroborating that the observed antiglioma effect of the NDI/2DG combined treatment was indeed based on LMP and glycolysis block. Based on these results, we concluded that NDI-triggered LMP caused initial mitochondrial damage, which was further increased by 2DG causing the lack of glycolytic ATP
required to maintain mitochondrial health. This created a positive feedback loop of mitochondrial dysfunction, ATP loss, and ROS production, culminating in necrosis. Therefore, the combination of glycolysis inhibitors and LMP-inducing agents seems promising antiglioma strategy.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition
SP  - 213
EP  - 213
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6355
ER  - 

@conference{
author = "Paunović, Verica and Kosić, Milica and Arsikin-Csordas, Katarina and Firestone, Raymond A and Ristić, Biljana and Mirčić, Aleksandar and Petričević, Saša and Bošnjak, Mihajlo and Zogović, Nevena and Mandić, Miloš and Bumbaširević, Vladimir and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2019",
abstract = "During malignant transformation cells acquire changes in metabolism, signaling pathways as well as organelle content. The preferential use of aerobic glycolysis (Warburg effect), along with the increased number and volume of lysosomes can be viewed as glioma cells’ Achilles heels. In the present study, we aimed to examine the in vitro antiglioma effects of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-D-glucose (2DG).
NDI-triggered LMP and 2DG-mediated glycolysis block synergistically induced rapid ATP depletion, mitochondrial damage, and reactive oxygen species (ROS) production causing necrotic cell death of U251 glioma cells, but not primary astrocytes. Lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol partially prevented NDI/2DG-induced glioma cell death, thus implying the involvement of LMP and oxidative stress in the observed cytotoxicity. Likewise, LMP-inducing agent chloroquine
showed synergistic cytotoxic effect with 2DG. Similarly, glucose deprivation as well as other glycolytic inhibitors, iodoacetate and sodium fluoride, synergistically cooperated with NDI, further corroborating that the observed antiglioma effect of the NDI/2DG combined treatment was indeed based on LMP and glycolysis block. Based on these results, we concluded that NDI-triggered LMP caused initial mitochondrial damage, which was further increased by 2DG causing the lack of glycolytic ATP
required to maintain mitochondrial health. This created a positive feedback loop of mitochondrial dysfunction, ATP loss, and ROS production, culminating in necrosis. Therefore, the combination of glycolysis inhibitors and LMP-inducing agents seems promising antiglioma strategy.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition",
pages = "213-213",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6355"
}

Paunović, V., Kosić, M., Arsikin-Csordas, K., Firestone, R. A., Ristić, B., Mirčić, A., Petričević, S., Bošnjak, M., Zogović, N., Mandić, M., Bumbaširević, V., Trajković, V.,& Harhaji-Trajković, L.. (2019). Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 213-213.
https://hdl.handle.net/21.15107/rcub_ibiss_6355

Paunović V, Kosić M, Arsikin-Csordas K, Firestone RA, Ristić B, Mirčić A, Petričević S, Bošnjak M, Zogović N, Mandić M, Bumbaširević V, Trajković V, Harhaji-Trajković L. Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:213-213.
https://hdl.handle.net/21.15107/rcub_ibiss_6355 .

Paunović, Verica, Kosić, Milica, Arsikin-Csordas, Katarina, Firestone, Raymond A, Ristić, Biljana, Mirčić, Aleksandar, Petričević, Saša, Bošnjak, Mihajlo, Zogović, Nevena, Mandić, Miloš, Bumbaširević, Vladimir, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):213-213,
https://hdl.handle.net/21.15107/rcub_ibiss_6355 .

TY  - JOUR
AU  - Lalić, Ivana M.
AU  - Bichele, Rudolf
AU  - Repar, Anja
AU  - Despotović, Sanja Z.
AU  - Petričević, Saša
AU  - Laan, Martti
AU  - Peterson, Pärt
AU  - Westermann, Jürgen
AU  - Milićević, Živana
AU  - Mirkov, Ivana
AU  - Milićević, Novica M.
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0940960217301553?via%3Dihub
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29289711
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3020
AB  - It is well known that bacterial lipopolysaccharide (LPS) induces migration of several cellular populations within the spleen. However, there are no data about the impact of LPS on B and T lymphocytes present in the red pulp. Therefore, we used an experimental model in which we tested the effects of intravenously injected LPS on the molecular, cellular and structural changes of the spleen, with special reference to the red pulp lymphocytes. We discovered that LPS induced a massive relocation of B and T lymphocytes from the splenic red pulp, which was independent of the tumor necrosis factor receptor-1 signaling axis. Early after LPS treatment, quantitative real-time PCR analysis revealed the elevated levels of mRNA encoding numerous chemokines and proinflammatory cytokines (XCL1, CXCL9, CXCL10, CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, TNFα and LTα) which affect the navigation and activities of B and T lymphocytes in the lymphoid tissues. An extreme increase in mRNA levels for CCL20 was detected in the white pulp of the LPS-treated mice. The CCL20-expressing cells were localized in the PALS. Some smaller CCL20-expressing cells were evenly dispersed in the B cell zone. Thus, our study provides new knowledge of how microbial products could be involved in shaping the structure of lymphatic organs.
T2  - Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft
T1  - Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen
VL  - 216
DO  - 10.1016/j.aanat.2017.12.002
SP  - 125
EP  - 134
ER  - 

@article{
author = "Lalić, Ivana M. and Bichele, Rudolf and Repar, Anja and Despotović, Sanja Z. and Petričević, Saša and Laan, Martti and Peterson, Pärt and Westermann, Jürgen and Milićević, Živana and Mirkov, Ivana and Milićević, Novica M.",
year = "2018",
abstract = "It is well known that bacterial lipopolysaccharide (LPS) induces migration of several cellular populations within the spleen. However, there are no data about the impact of LPS on B and T lymphocytes present in the red pulp. Therefore, we used an experimental model in which we tested the effects of intravenously injected LPS on the molecular, cellular and structural changes of the spleen, with special reference to the red pulp lymphocytes. We discovered that LPS induced a massive relocation of B and T lymphocytes from the splenic red pulp, which was independent of the tumor necrosis factor receptor-1 signaling axis. Early after LPS treatment, quantitative real-time PCR analysis revealed the elevated levels of mRNA encoding numerous chemokines and proinflammatory cytokines (XCL1, CXCL9, CXCL10, CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, TNFα and LTα) which affect the navigation and activities of B and T lymphocytes in the lymphoid tissues. An extreme increase in mRNA levels for CCL20 was detected in the white pulp of the LPS-treated mice. The CCL20-expressing cells were localized in the PALS. Some smaller CCL20-expressing cells were evenly dispersed in the B cell zone. Thus, our study provides new knowledge of how microbial products could be involved in shaping the structure of lymphatic organs.",
journal = "Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft",
title = "Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen",
volume = "216",
doi = "10.1016/j.aanat.2017.12.002",
pages = "125-134"
}

Lalić, I. M., Bichele, R., Repar, A., Despotović, S. Z., Petričević, S., Laan, M., Peterson, P., Westermann, J., Milićević, Ž., Mirkov, I.,& Milićević, N. M.. (2018). Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen. in Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft, 216, 125-134.
https://doi.org/10.1016/j.aanat.2017.12.002

Lalić IM, Bichele R, Repar A, Despotović SZ, Petričević S, Laan M, Peterson P, Westermann J, Milićević Ž, Mirkov I, Milićević NM. Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen. in Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft. 2018;216:125-134.
doi:10.1016/j.aanat.2017.12.002 .

Lalić, Ivana M., Bichele, Rudolf, Repar, Anja, Despotović, Sanja Z., Petričević, Saša, Laan, Martti, Peterson, Pärt, Westermann, Jürgen, Milićević, Živana, Mirkov, Ivana, Milićević, Novica M., "Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen" in Annals of anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft, 216 (2018):125-134,
https://doi.org/10.1016/j.aanat.2017.12.002 . .