TY  - JOUR
AU  - Filipović, Dragana
AU  - Perić, Ivana
AU  - Costina, Victor
AU  - Stanisavljević, Andrijana
AU  - Gass, Peter
AU  - Findeisen, Peter
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9013
AB  - Aims: To examine the differences in the hippocampal proteome profiles of resilience or susceptibility to chronic social isolation (CSIS), animal model of depression, and to identify biomarkers that can distinguish the two. Main methods: Comparative subproteomic approach was used to identify changes in hippocampal cytosol and nonsynaptic mitochondria (NSM) of CSIS-resilient compared to CSIS-sensitive or control rats. The resilient and sensitive phenotypes of CSIS rats were distinguished based on their sucrose preference values. Selected proteins were validated by Western blot or immunofluorescence. Key findings: Predominantly down-regulated processes such as cytosolic cytoskeleton organization, the calcium signaling pathway, ubiquitin proteasome degradation, redox system, malate/aspartate shuttling and glutamate metabolism in CSIS-resilient compared to CSIS-sensitive rats were found. Decreased protein expression of glycolytic enzymes with simultaneous increased expression of Aco2 involved in tricarboxylic acid cycle and expression of several subunits composing oxidative phosphorylation involved enzymes (Uqcrc2, Atp5f1a, Atp5f1b) were found, indicating shift in energy production from glycolysis to oxidative phosphorylation in NSM. The four-fold higher level of mitochondrial glyceraldehyde-3-phosphate dehydrogenase of resilient rats indicated its transfer from the cytosol to the NSM. An increased level of transketolase along with the reduced pyruvate kinase level suggested an activated pentose phosphate pathway in CSIS-resilient relative to control rats. Cytosolic up-regulated CSIS proteins were implicated in antioxidative and proteasomal systems, while down-regulated NSM protein was involved in oxidative phosphorylation. Significance: The identified altered activated pathways and potential biomarkers enhance understanding of molecular mechanisms underlying resilience or susceptibility to CSIS, crucial in developing new therapeutic strategies.
T2  - Life Sciences
T1  - Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria
VL  - 254
SP  - 117790
DO  - 10.1016/j.lfs.2020.117790
ER  - 

@article{
author = "Filipović, Dragana and Perić, Ivana and Costina, Victor and Stanisavljević, Andrijana and Gass, Peter and Findeisen, Peter",
year = "2020",
abstract = "Aims: To examine the differences in the hippocampal proteome profiles of resilience or susceptibility to chronic social isolation (CSIS), animal model of depression, and to identify biomarkers that can distinguish the two. Main methods: Comparative subproteomic approach was used to identify changes in hippocampal cytosol and nonsynaptic mitochondria (NSM) of CSIS-resilient compared to CSIS-sensitive or control rats. The resilient and sensitive phenotypes of CSIS rats were distinguished based on their sucrose preference values. Selected proteins were validated by Western blot or immunofluorescence. Key findings: Predominantly down-regulated processes such as cytosolic cytoskeleton organization, the calcium signaling pathway, ubiquitin proteasome degradation, redox system, malate/aspartate shuttling and glutamate metabolism in CSIS-resilient compared to CSIS-sensitive rats were found. Decreased protein expression of glycolytic enzymes with simultaneous increased expression of Aco2 involved in tricarboxylic acid cycle and expression of several subunits composing oxidative phosphorylation involved enzymes (Uqcrc2, Atp5f1a, Atp5f1b) were found, indicating shift in energy production from glycolysis to oxidative phosphorylation in NSM. The four-fold higher level of mitochondrial glyceraldehyde-3-phosphate dehydrogenase of resilient rats indicated its transfer from the cytosol to the NSM. An increased level of transketolase along with the reduced pyruvate kinase level suggested an activated pentose phosphate pathway in CSIS-resilient relative to control rats. Cytosolic up-regulated CSIS proteins were implicated in antioxidative and proteasomal systems, while down-regulated NSM protein was involved in oxidative phosphorylation. Significance: The identified altered activated pathways and potential biomarkers enhance understanding of molecular mechanisms underlying resilience or susceptibility to CSIS, crucial in developing new therapeutic strategies.",
journal = "Life Sciences",
title = "Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria",
volume = "254",
pages = "117790",
doi = "10.1016/j.lfs.2020.117790"
}

Filipović, D., Perić, I., Costina, V., Stanisavljević, A., Gass, P.,& Findeisen, P.. (2020). Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria. in Life Sciences, 254, 117790.
https://doi.org/10.1016/j.lfs.2020.117790

Filipović D, Perić I, Costina V, Stanisavljević A, Gass P, Findeisen P. Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria. in Life Sciences. 2020;254:117790.
doi:10.1016/j.lfs.2020.117790 .

Filipović, Dragana, Perić, Ivana, Costina, Victor, Stanisavljević, Andrijana, Gass, Peter, Findeisen, Peter, "Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria" in Life Sciences, 254 (2020):117790,
https://doi.org/10.1016/j.lfs.2020.117790 . .

TY  - JOUR
AU  - Perić, Ivana
AU  - Costina, Victor
AU  - Findeisen, Peter
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9721
AB  - Tianeptine (Tian) has been widely used in treating mood and anxiety disorders, and recently as a nootropic to improve cognitive performance. However, its mechanisms of action are insufficiently clear. We used a comparative proteomic approach to identify sub-proteome changes in hippocampal cytosol and non-synaptic mitochondria (NSM) following chronic Tian treatment (3 weeks, 10 mg/kg/day) of adult male Wistar rats and rats exposed to chronic social isolation stress (CSIS) (6 weeks), an animal model of depression. Behavioural assessment of depressive and anxiety-like behaviours was based on sucrose preference, forced swim test and marble burying. Selected differently expressed proteins were validated by Western blot and/or immunohistochemical analysis. Tian normalized the behavioural alternations induced by CSIS, indicating its antidepressant and anxiolytic efficacy. Proteomic data showed that Tian increased the expression of proteasome system elements and redox system enzymes, enhanced energy metabolism and increased glyceraldehyde-3-phosphate dehydrogenase expression bound to NSM in control rats. Tian-treatment of CSIS-stressed rats resulted in a minor suppression of the increase in proteasome elements and antioxidative enzymes, except for an increase in Cu-Zn superoxide dismutase, and increased the level of Lactate dehydrogenase. Our results indicate on an increased NSM functionality in controls and suppression of the CSIS-induced impairment of NSM functionality by Tian treatment as well as on the CSIS-caused discrepancy in Tian effects relative to controls.
T2  - Neuroscience
T1  - Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression
VL  - 451
SP  - 111
EP  - 125
DO  - 10.1016/j.neuroscience.2020.09.061
ER  - 

@article{
author = "Perić, Ivana and Costina, Victor and Findeisen, Peter and Gass, Peter and Filipović, Dragana",
year = "2020",
abstract = "Tianeptine (Tian) has been widely used in treating mood and anxiety disorders, and recently as a nootropic to improve cognitive performance. However, its mechanisms of action are insufficiently clear. We used a comparative proteomic approach to identify sub-proteome changes in hippocampal cytosol and non-synaptic mitochondria (NSM) following chronic Tian treatment (3 weeks, 10 mg/kg/day) of adult male Wistar rats and rats exposed to chronic social isolation stress (CSIS) (6 weeks), an animal model of depression. Behavioural assessment of depressive and anxiety-like behaviours was based on sucrose preference, forced swim test and marble burying. Selected differently expressed proteins were validated by Western blot and/or immunohistochemical analysis. Tian normalized the behavioural alternations induced by CSIS, indicating its antidepressant and anxiolytic efficacy. Proteomic data showed that Tian increased the expression of proteasome system elements and redox system enzymes, enhanced energy metabolism and increased glyceraldehyde-3-phosphate dehydrogenase expression bound to NSM in control rats. Tian-treatment of CSIS-stressed rats resulted in a minor suppression of the increase in proteasome elements and antioxidative enzymes, except for an increase in Cu-Zn superoxide dismutase, and increased the level of Lactate dehydrogenase. Our results indicate on an increased NSM functionality in controls and suppression of the CSIS-induced impairment of NSM functionality by Tian treatment as well as on the CSIS-caused discrepancy in Tian effects relative to controls.",
journal = "Neuroscience",
title = "Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression",
volume = "451",
pages = "111-125",
doi = "10.1016/j.neuroscience.2020.09.061"
}

Perić, I., Costina, V., Findeisen, P., Gass, P.,& Filipović, D.. (2020). Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression. in Neuroscience, 451, 111-125.
https://doi.org/10.1016/j.neuroscience.2020.09.061

Perić I, Costina V, Findeisen P, Gass P, Filipović D. Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression. in Neuroscience. 2020;451:111-125.
doi:10.1016/j.neuroscience.2020.09.061 .

Perić, Ivana, Costina, Victor, Findeisen, Peter, Gass, Peter, Filipović, Dragana, "Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression" in Neuroscience, 451 (2020):111-125,
https://doi.org/10.1016/j.neuroscience.2020.09.061 . .

TY  - JOUR
AU  - Perić, Ivana
AU  - Costina, Victor
AU  - Stanisavljević, Andrijana
AU  - Findeisen, Peter
AU  - Filipović, Dragana
PY  - 2018
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0028390818301461
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7913
AB  - Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to disease and treatment. As chronic social isolation (CSIS) is a valuable animal model for studying depression, we performed a comparative subproteomic study of rat hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15 mg/kg/day). Behaviorally, Flx treatment normalized the decreased sucrose preference and increased marble burying results resulting from CSIS, indicative of a FLX-induced attenuation of both anhedonia and anxiety. An analysis of cytosolic and nonsynaptic mitochondrial subproteome patterns revealed that CSIS resulted in down-regulation of proteins involved in mitochondrial transport and energy processes, primarily tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Chronic Flx treatment resulted in an up-regulation of CSIS-altered proteins and additional expression of other transporter and energy-involved proteins. Immunohistochemical analysis revealed hippocampal subregion-specific effects of CSIS and/or Flx treatment on selective protein expressions. (C) 2018 Elsevier Ltd. All rights reserved.
T2  - Neuropharmacology
T1  - Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action
VL  - 135
SP  - 268
EP  - 283
DO  - 10.1016/j.neuropharm.2018.03.034
ER  - 

@article{
author = "Perić, Ivana and Costina, Victor and Stanisavljević, Andrijana and Findeisen, Peter and Filipović, Dragana",
year = "2018",
abstract = "Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to disease and treatment. As chronic social isolation (CSIS) is a valuable animal model for studying depression, we performed a comparative subproteomic study of rat hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15 mg/kg/day). Behaviorally, Flx treatment normalized the decreased sucrose preference and increased marble burying results resulting from CSIS, indicative of a FLX-induced attenuation of both anhedonia and anxiety. An analysis of cytosolic and nonsynaptic mitochondrial subproteome patterns revealed that CSIS resulted in down-regulation of proteins involved in mitochondrial transport and energy processes, primarily tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Chronic Flx treatment resulted in an up-regulation of CSIS-altered proteins and additional expression of other transporter and energy-involved proteins. Immunohistochemical analysis revealed hippocampal subregion-specific effects of CSIS and/or Flx treatment on selective protein expressions. (C) 2018 Elsevier Ltd. All rights reserved.",
journal = "Neuropharmacology",
title = "Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action",
volume = "135",
pages = "268-283",
doi = "10.1016/j.neuropharm.2018.03.034"
}

Perić, I., Costina, V., Stanisavljević, A., Findeisen, P.,& Filipović, D.. (2018). Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action. in Neuropharmacology, 135, 268-283.
https://doi.org/10.1016/j.neuropharm.2018.03.034

Perić I, Costina V, Stanisavljević A, Findeisen P, Filipović D. Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action. in Neuropharmacology. 2018;135:268-283.
doi:10.1016/j.neuropharm.2018.03.034 .

Perić, Ivana, Costina, Victor, Stanisavljević, Andrijana, Findeisen, Peter, Filipović, Dragana, "Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action" in Neuropharmacology, 135 (2018):268-283,
https://doi.org/10.1016/j.neuropharm.2018.03.034 . .

TY  - JOUR
AU  - Filipović, Dragana
AU  - Costina, Victor
AU  - Perić, Ivana
AU  - Stanisavljević, Andrijana
AU  - Findeisen, Peter
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1441
AB  - Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15 mg/kg) was administered daily to adult male Wistar rats for 3 weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. (C) 2017 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria
VL  - 1659
SP  - 41
EP  - 54
DO  - 10.1016/j.brainres.2017.01.025
ER  - 

@article{
author = "Filipović, Dragana and Costina, Victor and Perić, Ivana and Stanisavljević, Andrijana and Findeisen, Peter",
year = "2017",
abstract = "Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15 mg/kg) was administered daily to adult male Wistar rats for 3 weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. (C) 2017 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria",
volume = "1659",
pages = "41-54",
doi = "10.1016/j.brainres.2017.01.025"
}

Filipović, D., Costina, V., Perić, I., Stanisavljević, A.,& Findeisen, P.. (2017). Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria. in Brain Research, 1659, 41-54.
https://doi.org/10.1016/j.brainres.2017.01.025

Filipović D, Costina V, Perić I, Stanisavljević A, Findeisen P. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria. in Brain Research. 2017;1659:41-54.
doi:10.1016/j.brainres.2017.01.025 .

Filipović, Dragana, Costina, Victor, Perić, Ivana, Stanisavljević, Andrijana, Findeisen, Peter, "Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria" in Brain Research, 1659 (2017):41-54,
https://doi.org/10.1016/j.brainres.2017.01.025 . .