TY  - JOUR
AU  - Filipović, Dragana
AU  - Novak, Božidar
AU  - Xiao, Jinqiu
AU  - Tadić, Predrag
AU  - Turck, Christoph W.
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13084
AB  - Chronic social isolation (CSIS) generates two stress-related phenotypes: resilience and susceptibility. However, the molecular mechanisms underlying CSIS resilience remain unclear. We identified altered proteome components and biochemical pathways and processes in the prefrontal cortex cytosolic fraction in CSIS-resilient rats compared to CSIS-susceptible and control rats using liquid chromatography coupled with tandem mass spectrometry followed by label-free quantification and STRING bioinformatics. A sucrose preference test was performed to distinguish rat phenotypes. Potential predictive proteins discriminating between the CSIS-resilient and CSIS-susceptible groups were identified using machine learning (ML) algorithms: support vector machine-based sequential feature selection and random forest-based feature importance scores. Predominantly, decreased levels of some glycolytic enzymes, G protein-coupled receptor proteins, the Ras subfamily of GTPases proteins, and antioxidant proteins were found in the CSIS-resilient vs. CSIS-susceptible groups. Altered levels of Gapdh, microtubular, cytoskeletal, and calcium-binding proteins were identified between the two phenotypes. Increased levels of proteins involved in GABA synthesis, the proteasome system, nitrogen metabolism, and chaperone-mediated protein folding were identified. Predictive proteins make CSIS-resilient vs. CSIS-susceptible groups linearly separable, whereby a 100% validation accuracy was achieved by ML models. The overall ratio of significantly up- and downregulated cytosolic proteins suggests adaptive cellular alterations as part of the stress-coping process specific for the CSIS-resilient phenotype.
T2  - International Journal of Molecular Sciences
T1  - Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats
VL  - 25
IS  - 5
SP  - 3026
DO  - 10.3390/ijms25053026
ER  - 

@article{
author = "Filipović, Dragana and Novak, Božidar and Xiao, Jinqiu and Tadić, Predrag and Turck, Christoph W.",
year = "2024",
abstract = "Chronic social isolation (CSIS) generates two stress-related phenotypes: resilience and susceptibility. However, the molecular mechanisms underlying CSIS resilience remain unclear. We identified altered proteome components and biochemical pathways and processes in the prefrontal cortex cytosolic fraction in CSIS-resilient rats compared to CSIS-susceptible and control rats using liquid chromatography coupled with tandem mass spectrometry followed by label-free quantification and STRING bioinformatics. A sucrose preference test was performed to distinguish rat phenotypes. Potential predictive proteins discriminating between the CSIS-resilient and CSIS-susceptible groups were identified using machine learning (ML) algorithms: support vector machine-based sequential feature selection and random forest-based feature importance scores. Predominantly, decreased levels of some glycolytic enzymes, G protein-coupled receptor proteins, the Ras subfamily of GTPases proteins, and antioxidant proteins were found in the CSIS-resilient vs. CSIS-susceptible groups. Altered levels of Gapdh, microtubular, cytoskeletal, and calcium-binding proteins were identified between the two phenotypes. Increased levels of proteins involved in GABA synthesis, the proteasome system, nitrogen metabolism, and chaperone-mediated protein folding were identified. Predictive proteins make CSIS-resilient vs. CSIS-susceptible groups linearly separable, whereby a 100% validation accuracy was achieved by ML models. The overall ratio of significantly up- and downregulated cytosolic proteins suggests adaptive cellular alterations as part of the stress-coping process specific for the CSIS-resilient phenotype.",
journal = "International Journal of Molecular Sciences",
title = "Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats",
volume = "25",
number = "5",
pages = "3026",
doi = "10.3390/ijms25053026"
}

Filipović, D., Novak, B., Xiao, J., Tadić, P.,& Turck, C. W.. (2024). Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats. in International Journal of Molecular Sciences, 25(5), 3026.
https://doi.org/10.3390/ijms25053026

Filipović D, Novak B, Xiao J, Tadić P, Turck CW. Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats. in International Journal of Molecular Sciences. 2024;25(5):3026.
doi:10.3390/ijms25053026 .

Filipović, Dragana, Novak, Božidar, Xiao, Jinqiu, Tadić, Predrag, Turck, Christoph W., "Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats" in International Journal of Molecular Sciences, 25, no. 5 (2024):3026,
https://doi.org/10.3390/ijms25053026 . .

TY  - CONF
AU  - Filipović, Dragana
AU  - Turck, Christoph W.
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12258
AB  - Exposure to chronic social isolation (CSIS) and dysfunction of serotonin neurotransmission have been implicated in the etiology of major depressive disorder (MDD). Fluoxetine (Flx) has been widely used to treat MDD, however, its molecular mechanisms of action are not yet defined. Hence, we carried out a comparative label-free proteomic approach to identify sub-proteome changes in the prefrontal cortex (PFC) cytosol, non-synaptic mitochondrial (NSM), and synaptosomal-enriched fractions of adult male Wistar rats following chronic social isolation (CSIS) (6 weeks), a rat model of depression, and/or following Flx treatment in CSIS and control rats (15 mg/mL/day) (lasting 3 weeks of 6-weeks CSIS) using liquid chromatography coupled to tandem mass spectrometry. Our aim was to identify the changes in protein levels that enable the identification of (possible) biochemical pathways and processes of importance for the development of depressive-like behavior and the efficacy of Flx treatments. Behavior was assessed with sucrose preference and forced swim tests. In controls, Flx downregulated the proteins involved in endocytosis and vesicle-mediated transport, while predominantly upregulating proteins involved in the microtubule cytoskeleton, intracellular calcium homeostasis, an enzyme linking the glycolytic pathway to the citric acid cycle in NSM, and exocytosis. CSIS affected the PFC proteome by downregulating the proteins involved in proteasome pathway, glutathione antioxidative system, synaptic vesicle cycle, and endocytosis while upregulating the protein levels of enzymes participating in oxidative phosphorylation 1,2. CSIS compromised mitochondrial membrane integrity, as assessed by cytochrome c levels in the cytosol. Effective Flx treatment in CSIS rats resulted in increased synaptic vesicle dynamic, plasticity, and mitochondrial functionality and a suppression of CSIS-induced impairment of these processes 1,2. Our data provide the basis for establishing a marker panel for CSIS-induced depression and effective Flx treatment and highlight the role of NSM and synaptosomal proteins involved in various biochemical pathways as novel investigative protein targets.
PB  - Kragujevac : Faculty of Science, University of Kragujevac
C3  - SePA : VI Symposium of a Serbian proteomic society: „Discussion and Application of New Methods of Proteomics“ : Book of abstracts
T1  - Chronic fluoxetine treatment of socially isolated rats modulates prefrontal cortex proteome
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12258
ER  - 

@conference{
author = "Filipović, Dragana and Turck, Christoph W.",
year = "2023",
abstract = "Exposure to chronic social isolation (CSIS) and dysfunction of serotonin neurotransmission have been implicated in the etiology of major depressive disorder (MDD). Fluoxetine (Flx) has been widely used to treat MDD, however, its molecular mechanisms of action are not yet defined. Hence, we carried out a comparative label-free proteomic approach to identify sub-proteome changes in the prefrontal cortex (PFC) cytosol, non-synaptic mitochondrial (NSM), and synaptosomal-enriched fractions of adult male Wistar rats following chronic social isolation (CSIS) (6 weeks), a rat model of depression, and/or following Flx treatment in CSIS and control rats (15 mg/mL/day) (lasting 3 weeks of 6-weeks CSIS) using liquid chromatography coupled to tandem mass spectrometry. Our aim was to identify the changes in protein levels that enable the identification of (possible) biochemical pathways and processes of importance for the development of depressive-like behavior and the efficacy of Flx treatments. Behavior was assessed with sucrose preference and forced swim tests. In controls, Flx downregulated the proteins involved in endocytosis and vesicle-mediated transport, while predominantly upregulating proteins involved in the microtubule cytoskeleton, intracellular calcium homeostasis, an enzyme linking the glycolytic pathway to the citric acid cycle in NSM, and exocytosis. CSIS affected the PFC proteome by downregulating the proteins involved in proteasome pathway, glutathione antioxidative system, synaptic vesicle cycle, and endocytosis while upregulating the protein levels of enzymes participating in oxidative phosphorylation 1,2. CSIS compromised mitochondrial membrane integrity, as assessed by cytochrome c levels in the cytosol. Effective Flx treatment in CSIS rats resulted in increased synaptic vesicle dynamic, plasticity, and mitochondrial functionality and a suppression of CSIS-induced impairment of these processes 1,2. Our data provide the basis for establishing a marker panel for CSIS-induced depression and effective Flx treatment and highlight the role of NSM and synaptosomal proteins involved in various biochemical pathways as novel investigative protein targets.",
publisher = "Kragujevac : Faculty of Science, University of Kragujevac",
journal = "SePA : VI Symposium of a Serbian proteomic society: „Discussion and Application of New Methods of Proteomics“ : Book of abstracts",
title = "Chronic fluoxetine treatment of socially isolated rats modulates prefrontal cortex proteome",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12258"
}

Filipović, D.,& Turck, C. W.. (2023). Chronic fluoxetine treatment of socially isolated rats modulates prefrontal cortex proteome. in SePA : VI Symposium of a Serbian proteomic society: „Discussion and Application of New Methods of Proteomics“ : Book of abstracts
Kragujevac : Faculty of Science, University of Kragujevac..
https://hdl.handle.net/21.15107/rcub_vinar_12258

Filipović D, Turck CW. Chronic fluoxetine treatment of socially isolated rats modulates prefrontal cortex proteome. in SePA : VI Symposium of a Serbian proteomic society: „Discussion and Application of New Methods of Proteomics“ : Book of abstracts. 2023;.
https://hdl.handle.net/21.15107/rcub_vinar_12258 .

Filipović, Dragana, Turck, Christoph W., "Chronic fluoxetine treatment of socially isolated rats modulates prefrontal cortex proteome" in SePA : VI Symposium of a Serbian proteomic society: „Discussion and Application of New Methods of Proteomics“ : Book of abstracts (2023),
https://hdl.handle.net/21.15107/rcub_vinar_12258 .