TY  - JOUR
AU  - Virijević, Kristina
AU  - Spasojević, Nataša
AU  - Stefanović, Bojana
AU  - Ferizović, Harisa
AU  - Janković, Milica
AU  - Vasiljević, Perica
AU  - Dronjak, Slađana
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12934
AB  - Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats. The results show that unstressed WKY females exhibited hypolocomotion, decreased exploratory behavior, and an increase in the total grooming time. After exposure to CMS, WKY females displayed intensified grooming. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed signaling and inflammatory pathways in the hippocampus and mPFC. The findings indicate reduced BDNF and elevated levels levels of IL-1β in both brain structures and NLRP3 in the mPFC of unstressed WKY female rats. WKY rats subjected to CMS showed a further decrease in BDNF levels and increased IL-1β and NLRP3 in these brain structures. WKY showed reduced pERK1/2 and increased pp38 levels in both brain structures, while CMS revealed a further increase of pp38 in WKY in these brain structures. Expressions of p110β and pAKT were decreased in the hippocampus and mPFC of WKY rats. The CMS further suppressed p110 and the downstream AKT phosphorylation in the hippocampus, but did not affect the p110 and pAKT in the mPFC. Our findings indicate behavioral and molecular differences in genetically vulnerable WKY female rats and in their response to CMS that may be involved in TRD.
T2  - Neuroscience Letters
T1  - Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats
VL  - 825
SP  - 137709
DO  - 10.1016/j.neulet.2024.137709
ER  - 

@article{
author = "Virijević, Kristina and Spasojević, Nataša and Stefanović, Bojana and Ferizović, Harisa and Janković, Milica and Vasiljević, Perica and Dronjak, Slađana",
year = "2024",
abstract = "Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats. The results show that unstressed WKY females exhibited hypolocomotion, decreased exploratory behavior, and an increase in the total grooming time. After exposure to CMS, WKY females displayed intensified grooming. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed signaling and inflammatory pathways in the hippocampus and mPFC. The findings indicate reduced BDNF and elevated levels levels of IL-1β in both brain structures and NLRP3 in the mPFC of unstressed WKY female rats. WKY rats subjected to CMS showed a further decrease in BDNF levels and increased IL-1β and NLRP3 in these brain structures. WKY showed reduced pERK1/2 and increased pp38 levels in both brain structures, while CMS revealed a further increase of pp38 in WKY in these brain structures. Expressions of p110β and pAKT were decreased in the hippocampus and mPFC of WKY rats. The CMS further suppressed p110 and the downstream AKT phosphorylation in the hippocampus, but did not affect the p110 and pAKT in the mPFC. Our findings indicate behavioral and molecular differences in genetically vulnerable WKY female rats and in their response to CMS that may be involved in TRD.",
journal = "Neuroscience Letters",
title = "Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats",
volume = "825",
pages = "137709",
doi = "10.1016/j.neulet.2024.137709"
}

Virijević, K., Spasojević, N., Stefanović, B., Ferizović, H., Janković, M., Vasiljević, P.,& Dronjak, S.. (2024). Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats. in Neuroscience Letters, 825, 137709.
https://doi.org/10.1016/j.neulet.2024.137709

Virijević K, Spasojević N, Stefanović B, Ferizović H, Janković M, Vasiljević P, Dronjak S. Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats. in Neuroscience Letters. 2024;825:137709.
doi:10.1016/j.neulet.2024.137709 .

Virijević, Kristina, Spasojević, Nataša, Stefanović, Bojana, Ferizović, Harisa, Janković, Milica, Vasiljević, Perica, Dronjak, Slađana, "Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats" in Neuroscience Letters, 825 (2024):137709,
https://doi.org/10.1016/j.neulet.2024.137709 . .

TY  - CONF
AU  - Janković, Milica
AU  - Ferizović, Harisa
AU  - Spasojević, Nataša
AU  - Stefanović, Bojana
AU  - Virijević, Kristina
AU  - Dronjak, Slađana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11059
AB  - Modulating the endocannabinoid system is emerging as a promising approach for treating various inflammatory, neurodegenerative, and psychiatric disorders. Major depressive disorder is a prevalent cause of disability worldwide, affecting up to 6% of the population and posing significant health and economic challenges. Since the existing antidepressant treatments are often insufficient, the endocannabinoid system presents an attractive target for potential therapies. To explore this possibility, two-month-old Wistar rats of both sexes were subjected to chronic unpredictable stress (CUS) for six weeks. During the last two weeks of stress protocol rats were injected with either a fatty acid amide hydrolase inhibitor, URB597 (i.p. 0.3 mg/kg), or a vehicle. At the end of the sixth week sucrose intake test was used to assess depressive-like behavior. After sacrificing the animals, Western blot analysis was used to determine the levels of brain-derived neurotrophic factor (BDNF) protein and levels of pro-inflammatory cytokine IL-1β in medial prefrontal cortex. The CUS exposure induced anhedonia in both female and male rats, and URB597 treatment alleviated these symptoms. Moreover, CUS increased the levels of IL1-β in the mPFC of both sexes. Stressed animals that have received URB597 had decreased levels of IL1-β structures compared to the animals receiving only vehicle. CUSexposed male and female rats also had lower levels of BDNF in the mPFC, but URB597 restored BDNF levels in female rats to those observed in control animals. Taken together, these findings suggest that URB597 may have antidepressant effects through reducing neuroinflammation and restoring BDNF levels in mPFC.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Fatty acid amide hydrolase inhibitor URB597 shows antidepressant effects through reduction of neuroinflammation and restoration of BDNF levels in mPFC of chronically stressed rats
SP  - 118
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11059
ER  - 

@conference{
author = "Janković, Milica and Ferizović, Harisa and Spasojević, Nataša and Stefanović, Bojana and Virijević, Kristina and Dronjak, Slađana",
year = "2023",
abstract = "Modulating the endocannabinoid system is emerging as a promising approach for treating various inflammatory, neurodegenerative, and psychiatric disorders. Major depressive disorder is a prevalent cause of disability worldwide, affecting up to 6% of the population and posing significant health and economic challenges. Since the existing antidepressant treatments are often insufficient, the endocannabinoid system presents an attractive target for potential therapies. To explore this possibility, two-month-old Wistar rats of both sexes were subjected to chronic unpredictable stress (CUS) for six weeks. During the last two weeks of stress protocol rats were injected with either a fatty acid amide hydrolase inhibitor, URB597 (i.p. 0.3 mg/kg), or a vehicle. At the end of the sixth week sucrose intake test was used to assess depressive-like behavior. After sacrificing the animals, Western blot analysis was used to determine the levels of brain-derived neurotrophic factor (BDNF) protein and levels of pro-inflammatory cytokine IL-1β in medial prefrontal cortex. The CUS exposure induced anhedonia in both female and male rats, and URB597 treatment alleviated these symptoms. Moreover, CUS increased the levels of IL1-β in the mPFC of both sexes. Stressed animals that have received URB597 had decreased levels of IL1-β structures compared to the animals receiving only vehicle. CUSexposed male and female rats also had lower levels of BDNF in the mPFC, but URB597 restored BDNF levels in female rats to those observed in control animals. Taken together, these findings suggest that URB597 may have antidepressant effects through reducing neuroinflammation and restoring BDNF levels in mPFC.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Fatty acid amide hydrolase inhibitor URB597 shows antidepressant effects through reduction of neuroinflammation and restoration of BDNF levels in mPFC of chronically stressed rats",
pages = "118",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11059"
}

Janković, M., Ferizović, H., Spasojević, N., Stefanović, B., Virijević, K.,& Dronjak, S.. (2023). Fatty acid amide hydrolase inhibitor URB597 shows antidepressant effects through reduction of neuroinflammation and restoration of BDNF levels in mPFC of chronically stressed rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 118.
https://hdl.handle.net/21.15107/rcub_vinar_11059

Janković M, Ferizović H, Spasojević N, Stefanović B, Virijević K, Dronjak S. Fatty acid amide hydrolase inhibitor URB597 shows antidepressant effects through reduction of neuroinflammation and restoration of BDNF levels in mPFC of chronically stressed rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:118.
https://hdl.handle.net/21.15107/rcub_vinar_11059 .

Janković, Milica, Ferizović, Harisa, Spasojević, Nataša, Stefanović, Bojana, Virijević, Kristina, Dronjak, Slađana, "Fatty acid amide hydrolase inhibitor URB597 shows antidepressant effects through reduction of neuroinflammation and restoration of BDNF levels in mPFC of chronically stressed rats" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):118,
https://hdl.handle.net/21.15107/rcub_vinar_11059 .

TY  - CONF
AU  - Virijević, Kristina
AU  - Spasojević, Nataša
AU  - Stefanović, Bojana
AU  - Ferizović, Harisa
AU  - Janković, Milica
AU  - Dronjak, Slađana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11053
AB  - Stress is a major precipitant of depression, the hippocampus (HPC) and prefrontal cortex (PFC) is the main structures affected by depressive disorders. Women are twice more likely to experience depression than men. The WKY rat strain has long been established as a model of depression. Initially bred from the Wistar (WI) rat as the control strain for the spontaneously hypertensive rat, WKY rats demonstrate an exaggerated stress response compared to other strains. WKY strain fails to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) and is considered to be nonresponsive to antidepressant drugs. MAPK signaling pathway was most closely related to depression and antidepressant treatment. In the present study, we have examined the effects of CMS on behavior and p38 MAPK signaling in the hippocampus and the medial prefrontal cortex (mPFC) of female WKY rats. We used two very different behavioral tests: forced swim test (FST) and open field test (OFT). WKY unstressed controls exhibited increased immobility duration in the forced swim test and decreased activity in the open-field test compared to unstressed WI rats, while CMS did not further influence behavior. WKY showed increased expression of the p38 only in HPC and further exposure of WKY rats to CMS induces sustained-activation of p38 MAPK in this brain area. The present study demonstrated the brain region-specific protein signatures in the female WKY model with endogenous depression, providing novel insights into the pathogenesis of depression.
PB  - Belgrade : Serbian Neurocardiological Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Chronic mild stress induces sustained-activation of p38 MAPK signaling in the female WKY rats with endogenous depression
SP  - 84
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11053
ER  - 

@conference{
author = "Virijević, Kristina and Spasojević, Nataša and Stefanović, Bojana and Ferizović, Harisa and Janković, Milica and Dronjak, Slađana",
year = "2023",
abstract = "Stress is a major precipitant of depression, the hippocampus (HPC) and prefrontal cortex (PFC) is the main structures affected by depressive disorders. Women are twice more likely to experience depression than men. The WKY rat strain has long been established as a model of depression. Initially bred from the Wistar (WI) rat as the control strain for the spontaneously hypertensive rat, WKY rats demonstrate an exaggerated stress response compared to other strains. WKY strain fails to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) and is considered to be nonresponsive to antidepressant drugs. MAPK signaling pathway was most closely related to depression and antidepressant treatment. In the present study, we have examined the effects of CMS on behavior and p38 MAPK signaling in the hippocampus and the medial prefrontal cortex (mPFC) of female WKY rats. We used two very different behavioral tests: forced swim test (FST) and open field test (OFT). WKY unstressed controls exhibited increased immobility duration in the forced swim test and decreased activity in the open-field test compared to unstressed WI rats, while CMS did not further influence behavior. WKY showed increased expression of the p38 only in HPC and further exposure of WKY rats to CMS induces sustained-activation of p38 MAPK in this brain area. The present study demonstrated the brain region-specific protein signatures in the female WKY model with endogenous depression, providing novel insights into the pathogenesis of depression.",
publisher = "Belgrade : Serbian Neurocardiological Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Chronic mild stress induces sustained-activation of p38 MAPK signaling in the female WKY rats with endogenous depression",
pages = "84",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11053"
}

Virijević, K., Spasojević, N., Stefanović, B., Ferizović, H., Janković, M.,& Dronjak, S.. (2023). Chronic mild stress induces sustained-activation of p38 MAPK signaling in the female WKY rats with endogenous depression. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neurocardiological Society., 84.
https://hdl.handle.net/21.15107/rcub_vinar_11053

Virijević K, Spasojević N, Stefanović B, Ferizović H, Janković M, Dronjak S. Chronic mild stress induces sustained-activation of p38 MAPK signaling in the female WKY rats with endogenous depression. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:84.
https://hdl.handle.net/21.15107/rcub_vinar_11053 .

Virijević, Kristina, Spasojević, Nataša, Stefanović, Bojana, Ferizović, Harisa, Janković, Milica, Dronjak, Slađana, "Chronic mild stress induces sustained-activation of p38 MAPK signaling in the female WKY rats with endogenous depression" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):84,
https://hdl.handle.net/21.15107/rcub_vinar_11053 .

TY  - CONF
AU  - Virijević, Kristina
AU  - Spasojević, Nataša
AU  - Stefanović, Bojana
AU  - Ferizović, Harisa
AU  - Janković, Milica
AU  - Dronjak, Slađana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12630
AB  - Background: The neurobiology underlying depression has not yet been fully identified, but is thought to result from molecular and cellular abnormalities that interact with genetic and environmental factors. Depression is twice as prevalent in women as in men, however, females remain underrepresented in preclinical research. In addition to the neurotransmission theory of depression, the inflammatory processes and the disrupted signaling pathways also play a crucial role in the pathophysiology of depression. The WKY rat strain has long been established as a model of depression. These rats demonstrate an exaggerated response to stress compared to other strains. WKY strain fail to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) and considered to be nonresponsive to antidepressant drugs. The hippocampus and the medial prefrontal cortex (mPFC) are thought to be an important regions for depression. Brain-derived neurotrophic factor (BDNF) play a vital role in the pathophysiology of depression. BDNF-stimulated signaling cascades, including the phosphatidylinositol 3-kinase (PI3K)–/serine threonine kinase (Akt), also implicated in depression and treatment respons. In the present study, we have examined the effects of CMS on behavior and BDNF and PI3K/Akt signaling in the hippocampus and mPFC of female WKY rats.

Method: In the experiment, we used three months old Wistar (WI) and WKY female rats. Animals were divided in two groups: control and animals exposed to CMS for 6 weeks. On the last day of stress procedure, animals were tested in elevated plus maze to determine the levels of anxiety. Animals were then sacrificed and hippocampus and mPFC were isolated. Levels of BDNF and pAkt were determined by Western blot method. Data were analyzed using the two way ANOVA and Tuckey’s post-hoc test.

Results: WKY rats showed significantly decreased number of rearings (by 70%, p<0.01),decreased number of total arm entries (by 21%, p<0.05) and the time spent in the open arms (by 73%, p<0.001) of the elevated plus-maze compared to WI control group. WKY females had a significantly lower level of BDNF in the hippocampus (by 12%, p<0.05) and mPFC (by 16%, p<0.05) and pAkt (by 14%, p<0.01) only in mPFC as compared to the WI female rats. Exposure of WKY females to CMS enhanced an anxiety-like behavior and hypolomotion (decrease in number of rearings by 31%, p<0.05, number of total arm entries by 89%, p<0.001, and timevspent in the open arms by 92%, p<0.001), further down-expression of BDNF in both brain areas (in PFC: by 15%, p<0.001; in hippocampus: by 7%, p<0.05) and Akt phosphorylation in the mPFC (by 17%, p<0.05) as well as a decreased pAkt in the hippocampus (by 36%, p<0.001).

Conclusions: The difference in the balance of BDNF and PI3K/Akt signaling pathways may be relevant to the resistance of WKY rats to antidepressant drug treatment and may be useful for developing new targets for depression treatment, especially in females.
C3  - Neuroscience Applied
T1  - Dysregulation of BDNF and PI3K/Akt signaling in the brain of female Wistar-Kyoto rats exposed to chronic mild stress
VL  - 2
IS  - Supplement 2
SP  - 102596
DO  - 10.1016/j.nsa.2023.102596
ER  - 

@conference{
author = "Virijević, Kristina and Spasojević, Nataša and Stefanović, Bojana and Ferizović, Harisa and Janković, Milica and Dronjak, Slađana",
year = "2023",
abstract = "Background: The neurobiology underlying depression has not yet been fully identified, but is thought to result from molecular and cellular abnormalities that interact with genetic and environmental factors. Depression is twice as prevalent in women as in men, however, females remain underrepresented in preclinical research. In addition to the neurotransmission theory of depression, the inflammatory processes and the disrupted signaling pathways also play a crucial role in the pathophysiology of depression. The WKY rat strain has long been established as a model of depression. These rats demonstrate an exaggerated response to stress compared to other strains. WKY strain fail to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) and considered to be nonresponsive to antidepressant drugs. The hippocampus and the medial prefrontal cortex (mPFC) are thought to be an important regions for depression. Brain-derived neurotrophic factor (BDNF) play a vital role in the pathophysiology of depression. BDNF-stimulated signaling cascades, including the phosphatidylinositol 3-kinase (PI3K)–/serine threonine kinase (Akt), also implicated in depression and treatment respons. In the present study, we have examined the effects of CMS on behavior and BDNF and PI3K/Akt signaling in the hippocampus and mPFC of female WKY rats.

Method: In the experiment, we used three months old Wistar (WI) and WKY female rats. Animals were divided in two groups: control and animals exposed to CMS for 6 weeks. On the last day of stress procedure, animals were tested in elevated plus maze to determine the levels of anxiety. Animals were then sacrificed and hippocampus and mPFC were isolated. Levels of BDNF and pAkt were determined by Western blot method. Data were analyzed using the two way ANOVA and Tuckey’s post-hoc test.

Results: WKY rats showed significantly decreased number of rearings (by 70%, p<0.01),decreased number of total arm entries (by 21%, p<0.05) and the time spent in the open arms (by 73%, p<0.001) of the elevated plus-maze compared to WI control group. WKY females had a significantly lower level of BDNF in the hippocampus (by 12%, p<0.05) and mPFC (by 16%, p<0.05) and pAkt (by 14%, p<0.01) only in mPFC as compared to the WI female rats. Exposure of WKY females to CMS enhanced an anxiety-like behavior and hypolomotion (decrease in number of rearings by 31%, p<0.05, number of total arm entries by 89%, p<0.001, and timevspent in the open arms by 92%, p<0.001), further down-expression of BDNF in both brain areas (in PFC: by 15%, p<0.001; in hippocampus: by 7%, p<0.05) and Akt phosphorylation in the mPFC (by 17%, p<0.05) as well as a decreased pAkt in the hippocampus (by 36%, p<0.001).

Conclusions: The difference in the balance of BDNF and PI3K/Akt signaling pathways may be relevant to the resistance of WKY rats to antidepressant drug treatment and may be useful for developing new targets for depression treatment, especially in females.",
journal = "Neuroscience Applied",
title = "Dysregulation of BDNF and PI3K/Akt signaling in the brain of female Wistar-Kyoto rats exposed to chronic mild stress",
volume = "2",
number = "Supplement 2",
pages = "102596",
doi = "10.1016/j.nsa.2023.102596"
}

Virijević, K., Spasojević, N., Stefanović, B., Ferizović, H., Janković, M.,& Dronjak, S.. (2023). Dysregulation of BDNF and PI3K/Akt signaling in the brain of female Wistar-Kyoto rats exposed to chronic mild stress. in Neuroscience Applied, 2(Supplement 2), 102596.
https://doi.org/10.1016/j.nsa.2023.102596

Virijević K, Spasojević N, Stefanović B, Ferizović H, Janković M, Dronjak S. Dysregulation of BDNF and PI3K/Akt signaling in the brain of female Wistar-Kyoto rats exposed to chronic mild stress. in Neuroscience Applied. 2023;2(Supplement 2):102596.
doi:10.1016/j.nsa.2023.102596 .

Virijević, Kristina, Spasojević, Nataša, Stefanović, Bojana, Ferizović, Harisa, Janković, Milica, Dronjak, Slađana, "Dysregulation of BDNF and PI3K/Akt signaling in the brain of female Wistar-Kyoto rats exposed to chronic mild stress" in Neuroscience Applied, 2, no. Supplement 2 (2023):102596,
https://doi.org/10.1016/j.nsa.2023.102596 . .

TY  - JOUR
AU  - Ferizović, Harisa
AU  - Spasojević, Nataša
AU  - Puškaš, Nela
AU  - Stefanović, Bojana
AU  - Janković, Milica
AU  - Đelić, Ninoslav
AU  - Dronjak, Slađana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11385
AB  - Endocannabinoids act as a stress response system; simultaneously, the modulation of this system has emerged a novel approach for the therapy of cardiovascular disorders. We investigated the protective effects of the chronic administration of the fatty acid amide hydrolase inhibitor URB597 on morphology, pro-inflammatory and anti-inflammatory cytokine, the cytoplasm-nuclear distribution of JAK2/STAT3, and NF-κB and Nrf2/HO-1 signaling in the left ventricle of female and male rats exposed to chronic unpredictable stress. Our results show that URB597 treatment exhibits an antidepressant-like effect, decreases the heart/body weight ratio, prevents the hypertrophy of cardiomyocytes, and reduces the increased level of IL-6 in the wall of the left ventricle of stressed female and male rats. The phosphorylation levels of JAK2 and STAT3 in the ventricle of male rats treated with URB597 were declined, whereas in female rats the decrease of STAT3 was observed. In addition, URB597 reduced increased NF-κB in both females and males and increased the expression of Nrf2 and HO-1 protein in the cytosol of male rats, whereas did not affect their levels in females. Cardioprotective effects of URB597 could be linked to the ability to inhibit the JAK2 in males and the STAT3 inflammatory signaling pathways in both females and males.
T2  - Canadian Journal of Physiology and Pharmacology
T1  - URB597 attenuates stress-induced ventricular structural remodeling by modulating cytokines, NF-κB, and JAK2/STAT3 pathways in female and male rats
VL  - 101
IS  - 8
SP  - 400
EP  - 412
DO  - 10.1139/cjpp-2022-0535
ER  - 

@article{
author = "Ferizović, Harisa and Spasojević, Nataša and Puškaš, Nela and Stefanović, Bojana and Janković, Milica and Đelić, Ninoslav and Dronjak, Slađana",
year = "2023",
abstract = "Endocannabinoids act as a stress response system; simultaneously, the modulation of this system has emerged a novel approach for the therapy of cardiovascular disorders. We investigated the protective effects of the chronic administration of the fatty acid amide hydrolase inhibitor URB597 on morphology, pro-inflammatory and anti-inflammatory cytokine, the cytoplasm-nuclear distribution of JAK2/STAT3, and NF-κB and Nrf2/HO-1 signaling in the left ventricle of female and male rats exposed to chronic unpredictable stress. Our results show that URB597 treatment exhibits an antidepressant-like effect, decreases the heart/body weight ratio, prevents the hypertrophy of cardiomyocytes, and reduces the increased level of IL-6 in the wall of the left ventricle of stressed female and male rats. The phosphorylation levels of JAK2 and STAT3 in the ventricle of male rats treated with URB597 were declined, whereas in female rats the decrease of STAT3 was observed. In addition, URB597 reduced increased NF-κB in both females and males and increased the expression of Nrf2 and HO-1 protein in the cytosol of male rats, whereas did not affect their levels in females. Cardioprotective effects of URB597 could be linked to the ability to inhibit the JAK2 in males and the STAT3 inflammatory signaling pathways in both females and males.",
journal = "Canadian Journal of Physiology and Pharmacology",
title = "URB597 attenuates stress-induced ventricular structural remodeling by modulating cytokines, NF-κB, and JAK2/STAT3 pathways in female and male rats",
volume = "101",
number = "8",
pages = "400-412",
doi = "10.1139/cjpp-2022-0535"
}

Ferizović, H., Spasojević, N., Puškaš, N., Stefanović, B., Janković, M., Đelić, N.,& Dronjak, S.. (2023). URB597 attenuates stress-induced ventricular structural remodeling by modulating cytokines, NF-κB, and JAK2/STAT3 pathways in female and male rats. in Canadian Journal of Physiology and Pharmacology, 101(8), 400-412.
https://doi.org/10.1139/cjpp-2022-0535

Ferizović H, Spasojević N, Puškaš N, Stefanović B, Janković M, Đelić N, Dronjak S. URB597 attenuates stress-induced ventricular structural remodeling by modulating cytokines, NF-κB, and JAK2/STAT3 pathways in female and male rats. in Canadian Journal of Physiology and Pharmacology. 2023;101(8):400-412.
doi:10.1139/cjpp-2022-0535 .

Ferizović, Harisa, Spasojević, Nataša, Puškaš, Nela, Stefanović, Bojana, Janković, Milica, Đelić, Ninoslav, Dronjak, Slađana, "URB597 attenuates stress-induced ventricular structural remodeling by modulating cytokines, NF-κB, and JAK2/STAT3 pathways in female and male rats" in Canadian Journal of Physiology and Pharmacology, 101, no. 8 (2023):400-412,
https://doi.org/10.1139/cjpp-2022-0535 . .

TY  - JOUR
AU  - Ferizović, Harisa
AU  - Spasojević, Nataša
AU  - Janković, Milica
AU  - Stefanović, Bojana
AU  - Dronjak, Slađana
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13112
AB  - Introduction: The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS). Material and Methods: Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol. Catecholamines’ plasma levels and catecholamines’ levels in adrenal medulla were examined using Elabscience ELISA kits. Western blot analysis was used to detect the protein in the medulla. Results: The results of our experiment showed that adrenal weights and catecholamine of unstressed control were higher in females and that CUS induced further enlargement of adrenal glands and catecholamine content and its synthesis compared to male rats. CUS caused an increase of plasma norepinephrine and depletion of norepinephrine content as well as unchanged synthesis and degradation of catecholamine in the adrenal medulla of male rats. URB597 reduced enlarged adrenals and catecholamine content and its synthesis in stressed female rats. URB597 reduces increased plasma norepinephrine and restores its content in the adrenal medulla, unchanging the expression of enzyme synthesis, while reduced protein levels of monoamine oxidase A in male rats are exposed to CUS. Discussion: Our results support the role of endocannabinoids as an antistress mechanism that inhibits elevated adrenomedullary activation and promotes its recovery to baseline in both male and female stressed rats.
T2  - Pharmacology
T1  - Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats
VL  - 107
IS  - 1-2
SP  - 81
EP  - 89
DO  - 10.1159/000519332
ER  - 

@article{
author = "Ferizović, Harisa and Spasojević, Nataša and Janković, Milica and Stefanović, Bojana and Dronjak, Slađana",
year = "2022",
abstract = "Introduction: The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS). Material and Methods: Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol. Catecholamines’ plasma levels and catecholamines’ levels in adrenal medulla were examined using Elabscience ELISA kits. Western blot analysis was used to detect the protein in the medulla. Results: The results of our experiment showed that adrenal weights and catecholamine of unstressed control were higher in females and that CUS induced further enlargement of adrenal glands and catecholamine content and its synthesis compared to male rats. CUS caused an increase of plasma norepinephrine and depletion of norepinephrine content as well as unchanged synthesis and degradation of catecholamine in the adrenal medulla of male rats. URB597 reduced enlarged adrenals and catecholamine content and its synthesis in stressed female rats. URB597 reduces increased plasma norepinephrine and restores its content in the adrenal medulla, unchanging the expression of enzyme synthesis, while reduced protein levels of monoamine oxidase A in male rats are exposed to CUS. Discussion: Our results support the role of endocannabinoids as an antistress mechanism that inhibits elevated adrenomedullary activation and promotes its recovery to baseline in both male and female stressed rats.",
journal = "Pharmacology",
title = "Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats",
volume = "107",
number = "1-2",
pages = "81-89",
doi = "10.1159/000519332"
}

Ferizović, H., Spasojević, N., Janković, M., Stefanović, B.,& Dronjak, S.. (2022). Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats. in Pharmacology, 107(1-2), 81-89.
https://doi.org/10.1159/000519332

Ferizović H, Spasojević N, Janković M, Stefanović B, Dronjak S. Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats. in Pharmacology. 2022;107(1-2):81-89.
doi:10.1159/000519332 .

Ferizović, Harisa, Spasojević, Nataša, Janković, Milica, Stefanović, Bojana, Dronjak, Slađana, "Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats" in Pharmacology, 107, no. 1-2 (2022):81-89,
https://doi.org/10.1159/000519332 . .

TY  - CONF
AU  - Stefanović, Bojana
AU  - Spasojević, Nataša
AU  - Ferizović, Harisa
AU  - Janković, Milica
AU  - Vasiljević, Perica
AU  - Dronjak, Slađana
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12506
AB  - Istraživanja iz oblasti depresivnih poremećaja su sve više usmerena ka hipotezi da su oksidativni stres i inflamatorni procesi takođe uključeni u patogenezu depresije. Signalni put koji uključuje janus kinazu 2 (JAK2) i pretvarač signala i aktivator transkripcije 3 (STAT3) je povezan sa inflamacijom, a komponente ovog puta se eksprimiraju u različitim regionima mozga, posebno u hipokampusu. Cilj ovog rada bio je da se ispita uloga elemenata JAK2/STAT3 signalnog puta kod depresije izazvane hroničnim blagim stresom (CMS). U radu su korišćene ženke Wistar (W) i Wistar-Kyoto (WK) soja pacova. WK soj pokazuje neurondokrine promene, kao i promene u ponašanju slične depresiji, zbog čega se smatraju dobrim animalnim modelom endogene depresije. Odrasle W i WK ženke bile su izložene CMS u trajanju od 6 nedelja. Nakon ovog perioda jedinke su žrtvovane i izolovani su hipokampusi. Kvantitativna Western blot analiza naših rezultata je pokazala da je kod kontrolne WK grupe, u odnosu na kontrolnu W grupu, fosforilacija JAK2 i STAT3 u hipokampusu povećana, što ukazuje da je disregulacija ovog signalnog puta jedan od mogućih uzročnika simptoma depresije kod ovog soja. Hronični stres je dodatno povećao ekspresiju fosforilisane forme ovih proteina kod oba soja. Ova studija pružila je nove dokaze o učešću JAK2/STAT3 signalnog puta u patogenezi depresije i može nas usmeriti u nalaženju novih, efikasnijih terapija u lečenju rezistentne depresije.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka
T1  - Disregulacija JAK2/STAT3 signalnog puta u hipokampusu pacova sa genetski predisponiranim depresivnim ponašanjem
SP  - 359
EP  - 359
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12506
ER  - 

@conference{
author = "Stefanović, Bojana and Spasojević, Nataša and Ferizović, Harisa and Janković, Milica and Vasiljević, Perica and Dronjak, Slađana",
year = "2022",
abstract = "Istraživanja iz oblasti depresivnih poremećaja su sve više usmerena ka hipotezi da su oksidativni stres i inflamatorni procesi takođe uključeni u patogenezu depresije. Signalni put koji uključuje janus kinazu 2 (JAK2) i pretvarač signala i aktivator transkripcije 3 (STAT3) je povezan sa inflamacijom, a komponente ovog puta se eksprimiraju u različitim regionima mozga, posebno u hipokampusu. Cilj ovog rada bio je da se ispita uloga elemenata JAK2/STAT3 signalnog puta kod depresije izazvane hroničnim blagim stresom (CMS). U radu su korišćene ženke Wistar (W) i Wistar-Kyoto (WK) soja pacova. WK soj pokazuje neurondokrine promene, kao i promene u ponašanju slične depresiji, zbog čega se smatraju dobrim animalnim modelom endogene depresije. Odrasle W i WK ženke bile su izložene CMS u trajanju od 6 nedelja. Nakon ovog perioda jedinke su žrtvovane i izolovani su hipokampusi. Kvantitativna Western blot analiza naših rezultata je pokazala da je kod kontrolne WK grupe, u odnosu na kontrolnu W grupu, fosforilacija JAK2 i STAT3 u hipokampusu povećana, što ukazuje da je disregulacija ovog signalnog puta jedan od mogućih uzročnika simptoma depresije kod ovog soja. Hronični stres je dodatno povećao ekspresiju fosforilisane forme ovih proteina kod oba soja. Ova studija pružila je nove dokaze o učešću JAK2/STAT3 signalnog puta u patogenezi depresije i može nas usmeriti u nalaženju novih, efikasnijih terapija u lečenju rezistentne depresije.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka",
title = "Disregulacija JAK2/STAT3 signalnog puta u hipokampusu pacova sa genetski predisponiranim depresivnim ponašanjem",
pages = "359-359",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12506"
}

Stefanović, B., Spasojević, N., Ferizović, H., Janković, M., Vasiljević, P.,& Dronjak, S.. (2022). Disregulacija JAK2/STAT3 signalnog puta u hipokampusu pacova sa genetski predisponiranim depresivnim ponašanjem. in Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka
Beograd : Srpsko biološko društvo., 359-359.
https://hdl.handle.net/21.15107/rcub_vinar_12506

Stefanović B, Spasojević N, Ferizović H, Janković M, Vasiljević P, Dronjak S. Disregulacija JAK2/STAT3 signalnog puta u hipokampusu pacova sa genetski predisponiranim depresivnim ponašanjem. in Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka. 2022;:359-359.
https://hdl.handle.net/21.15107/rcub_vinar_12506 .

Stefanović, Bojana, Spasojević, Nataša, Ferizović, Harisa, Janković, Milica, Vasiljević, Perica, Dronjak, Slađana, "Disregulacija JAK2/STAT3 signalnog puta u hipokampusu pacova sa genetski predisponiranim depresivnim ponašanjem" in Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka (2022):359-359,
https://hdl.handle.net/21.15107/rcub_vinar_12506 .

TY  - CONF
AU  - Spasojević, Nataša
AU  - Stefanović, Bojana
AU  - Ferizović, Harisa
AU  - Janković, Milica
AU  - Dronjak, Slađana
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12505
AB  - Brojni dokazi ukazuju da socijalna izolacija može imati dugoročne efekte na ponašanje i u odgovoru na stres. Wistar-Kyoto (WK) soj pacova se smatra dobrim animalnim modelom rezistentne depresije jer su, za razliku od Wistar (W) soja, nakon izlaganja stresu neosetljivi na terapiju antidepresivima. U ovoj studiji smo izlagali ženke WK i W soja pacova hroničnom blagom stresu (CMS) u trajanju od 6 nedelja. Kontrolne životinje su bile u grupi po 3 jedinke, dok je CMS grupa pacova bila izolovana 3 nedelje pre početka CMS procedure do kraja eksperimenta. Znaci anhedonije su tokom 6 nedelja bili procenjivani testom unosa saharoze, dok je stepen anksioznosti utvrđen testom izdignutog plus lavirinta na kraju eksperimenta. Kontrolna WK grupa je pokazivala od prve do poslednje nedelje eksperimenta smanjen unos saharoze, hipolokomociju i smanjen broj ulaza u otvorene krake u odnosu na kontrolnu W grupu, što potvrđuje da ovaj soj i u odsustvu stresa pokazuje simptome depresije i anksioznosti. Izlaganje CMS je dovelo do dodatnih razlika između sojeva u unosu saharoze. Izolacija u trajanju od 3 nedelje pre CMS dovela je kod oba soja do povećanja unosa saharoze, što može ukazati na povećanu potrebu za zadovoljstvima. Hronični blagi stres je samo kod W soja doveo do znakova anhedonije, dok su ženke WK soja i nakon 6 nedelja CMS imale povećan unos saharoze. Ovi rezultati su relevantni za razumevanje načina na koji socijalna izolacija doprinosi osetljivosti pojedinca na poremećaje povezane sa stresom tokom života.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka
T1  - Uticaj hroničnog blagog stresa na ponašanje Wistar-Kyoto soja pacova kao animalnog modela rezistentne depresije
SP  - 380
EP  - 380
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12505
ER  - 

@conference{
author = "Spasojević, Nataša and Stefanović, Bojana and Ferizović, Harisa and Janković, Milica and Dronjak, Slađana",
year = "2022",
abstract = "Brojni dokazi ukazuju da socijalna izolacija može imati dugoročne efekte na ponašanje i u odgovoru na stres. Wistar-Kyoto (WK) soj pacova se smatra dobrim animalnim modelom rezistentne depresije jer su, za razliku od Wistar (W) soja, nakon izlaganja stresu neosetljivi na terapiju antidepresivima. U ovoj studiji smo izlagali ženke WK i W soja pacova hroničnom blagom stresu (CMS) u trajanju od 6 nedelja. Kontrolne životinje su bile u grupi po 3 jedinke, dok je CMS grupa pacova bila izolovana 3 nedelje pre početka CMS procedure do kraja eksperimenta. Znaci anhedonije su tokom 6 nedelja bili procenjivani testom unosa saharoze, dok je stepen anksioznosti utvrđen testom izdignutog plus lavirinta na kraju eksperimenta. Kontrolna WK grupa je pokazivala od prve do poslednje nedelje eksperimenta smanjen unos saharoze, hipolokomociju i smanjen broj ulaza u otvorene krake u odnosu na kontrolnu W grupu, što potvrđuje da ovaj soj i u odsustvu stresa pokazuje simptome depresije i anksioznosti. Izlaganje CMS je dovelo do dodatnih razlika između sojeva u unosu saharoze. Izolacija u trajanju od 3 nedelje pre CMS dovela je kod oba soja do povećanja unosa saharoze, što može ukazati na povećanu potrebu za zadovoljstvima. Hronični blagi stres je samo kod W soja doveo do znakova anhedonije, dok su ženke WK soja i nakon 6 nedelja CMS imale povećan unos saharoze. Ovi rezultati su relevantni za razumevanje načina na koji socijalna izolacija doprinosi osetljivosti pojedinca na poremećaje povezane sa stresom tokom života.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka",
title = "Uticaj hroničnog blagog stresa na ponašanje Wistar-Kyoto soja pacova kao animalnog modela rezistentne depresije",
pages = "380-380",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12505"
}

Spasojević, N., Stefanović, B., Ferizović, H., Janković, M.,& Dronjak, S.. (2022). Uticaj hroničnog blagog stresa na ponašanje Wistar-Kyoto soja pacova kao animalnog modela rezistentne depresije. in Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka
Beograd : Srpsko biološko društvo., 380-380.
https://hdl.handle.net/21.15107/rcub_vinar_12505

Spasojević N, Stefanović B, Ferizović H, Janković M, Dronjak S. Uticaj hroničnog blagog stresa na ponašanje Wistar-Kyoto soja pacova kao animalnog modela rezistentne depresije. in Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka. 2022;:380-380.
https://hdl.handle.net/21.15107/rcub_vinar_12505 .

Spasojević, Nataša, Stefanović, Bojana, Ferizović, Harisa, Janković, Milica, Dronjak, Slađana, "Uticaj hroničnog blagog stresa na ponašanje Wistar-Kyoto soja pacova kao animalnog modela rezistentne depresije" in Treći kongres biologa Srbije : Osnovna i primenjena istraživanja, metodika nastave : Knjiga sažetaka (2022):380-380,
https://hdl.handle.net/21.15107/rcub_vinar_12505 .

TY  - JOUR
AU  - Janković, Milica
AU  - Spasojević, Nataša
AU  - Ferizović, Harisa
AU  - Stefanović, Bojana
AU  - Dronjak, Slađana
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10056
AB  - An increasing body of evidence shows significant sex differences in the mammalian brain in multiple behaviours and psychiatric and neurological diseases and as well as that the endocannabinoid system may differ between males and females. In this study we investigated sex differences in working, short-term and long-term memory and the expression of β2-adrenergic and D1- and D2-receptors in the mPFC and hippocampus, brain regions that are involved in stress response and memory modulation in rats exposed to the chronic unpredictable stress (CUS) and the potential beneficial effects of the chronic fatty acid amide hydrolase inhibitor URB597 treatment. Chronically stressed male rats had an improvement of working memory, while stressed females showed very low object-recognition abilities. On the other hand, animals of both sexes exhibited long-term memory impairment. Our results showed that CUS decreased the expression of β2-adrenoceptors in the mPFC and D1 receptors in the mPFC and hippocampus of male rats and decreased β2-adrenoceptors and D1- receptors in the hippocampus of female. URB597 treatment had a positive effect on the short-term memory of stressed animals of both sexes whereas failed to restore long-term memory and did not affect the protein levels β2-adrenoceptors and D1 receptors in the hippocampus of CUS female rats. The present results support that endocannabinoids induced long-term memory and neurochemical alternations which are sex dependent, suggesting sex specific treatment strategies of mental disorders.
T2  - Neuroscience Letters
T1  - Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β2-adrenergic and D1-dopamine receptors
VL  - 768
SP  - 136363
DO  - 10.1016/j.neulet.2021.136363
ER  - 

@article{
author = "Janković, Milica and Spasojević, Nataša and Ferizović, Harisa and Stefanović, Bojana and Dronjak, Slađana",
year = "2022",
abstract = "An increasing body of evidence shows significant sex differences in the mammalian brain in multiple behaviours and psychiatric and neurological diseases and as well as that the endocannabinoid system may differ between males and females. In this study we investigated sex differences in working, short-term and long-term memory and the expression of β2-adrenergic and D1- and D2-receptors in the mPFC and hippocampus, brain regions that are involved in stress response and memory modulation in rats exposed to the chronic unpredictable stress (CUS) and the potential beneficial effects of the chronic fatty acid amide hydrolase inhibitor URB597 treatment. Chronically stressed male rats had an improvement of working memory, while stressed females showed very low object-recognition abilities. On the other hand, animals of both sexes exhibited long-term memory impairment. Our results showed that CUS decreased the expression of β2-adrenoceptors in the mPFC and D1 receptors in the mPFC and hippocampus of male rats and decreased β2-adrenoceptors and D1- receptors in the hippocampus of female. URB597 treatment had a positive effect on the short-term memory of stressed animals of both sexes whereas failed to restore long-term memory and did not affect the protein levels β2-adrenoceptors and D1 receptors in the hippocampus of CUS female rats. The present results support that endocannabinoids induced long-term memory and neurochemical alternations which are sex dependent, suggesting sex specific treatment strategies of mental disorders.",
journal = "Neuroscience Letters",
title = "Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β2-adrenergic and D1-dopamine receptors",
volume = "768",
pages = "136363",
doi = "10.1016/j.neulet.2021.136363"
}

Janković, M., Spasojević, N., Ferizović, H., Stefanović, B.,& Dronjak, S.. (2022). Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β2-adrenergic and D1-dopamine receptors. in Neuroscience Letters, 768, 136363.
https://doi.org/10.1016/j.neulet.2021.136363

Janković M, Spasojević N, Ferizović H, Stefanović B, Dronjak S. Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β2-adrenergic and D1-dopamine receptors. in Neuroscience Letters. 2022;768:136363.
doi:10.1016/j.neulet.2021.136363 .

Janković, Milica, Spasojević, Nataša, Ferizović, Harisa, Stefanović, Bojana, Dronjak, Slađana, "Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β2-adrenergic and D1-dopamine receptors" in Neuroscience Letters, 768 (2022):136363,
https://doi.org/10.1016/j.neulet.2021.136363 . .

TY  - JOUR
AU  - Ferizović, Harisa
AU  - Spasojević, Nataša
AU  - Stefanović, Bojana
AU  - Janković, Milica
AU  - Dronjak, Slađana
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9007
AB  - The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats. The results show that CUS increases anxiety-like behaviors and that URB597 had an anxiolytic effect on chronically stressed animals of both sexes. CUS induced the expression of plasma interleukin – 6 (IL-6), interleukin – 10 (IL-10) and IL-6 in the spleen, whereas the expression of IL-10 was reduced in the spleen of both sexes. URB597 treatment did not cause changes in IL-6 in plasma or the spleen, whereas it increased IL-10 in the spleen in CUS animals of both sexes. CUS caused a significant depletion of noradrenaline content in the spleen of female rats and a reduction in noradrenaline uptake in the spleen of female rats, while stressed males had a small but insignificant decrease of splenic noradrenaline levels and an enhanced uptake. The FAAH inhibitor URB597 enhances reduced noradrenaline content, affecting its uptake directly at the level of the spleen. It gives rise to the possibility that endocannabinoids exert a neurorestorative effect on the sympathetic nerve system and cell-mediated immune responses in the spleen of chronically stressed rats.
T2  - International Immunopharmacology
T1  - The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats
VL  - 85
SP  - 106615
DO  - 10.1016/j.intimp.2020.106615
ER  - 

@article{
author = "Ferizović, Harisa and Spasojević, Nataša and Stefanović, Bojana and Janković, Milica and Dronjak, Slađana",
year = "2020",
abstract = "The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats. The results show that CUS increases anxiety-like behaviors and that URB597 had an anxiolytic effect on chronically stressed animals of both sexes. CUS induced the expression of plasma interleukin – 6 (IL-6), interleukin – 10 (IL-10) and IL-6 in the spleen, whereas the expression of IL-10 was reduced in the spleen of both sexes. URB597 treatment did not cause changes in IL-6 in plasma or the spleen, whereas it increased IL-10 in the spleen in CUS animals of both sexes. CUS caused a significant depletion of noradrenaline content in the spleen of female rats and a reduction in noradrenaline uptake in the spleen of female rats, while stressed males had a small but insignificant decrease of splenic noradrenaline levels and an enhanced uptake. The FAAH inhibitor URB597 enhances reduced noradrenaline content, affecting its uptake directly at the level of the spleen. It gives rise to the possibility that endocannabinoids exert a neurorestorative effect on the sympathetic nerve system and cell-mediated immune responses in the spleen of chronically stressed rats.",
journal = "International Immunopharmacology",
title = "The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats",
volume = "85",
pages = "106615",
doi = "10.1016/j.intimp.2020.106615"
}

Ferizović, H., Spasojević, N., Stefanović, B., Janković, M.,& Dronjak, S.. (2020). The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats. in International Immunopharmacology, 85, 106615.
https://doi.org/10.1016/j.intimp.2020.106615

Ferizović H, Spasojević N, Stefanović B, Janković M, Dronjak S. The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats. in International Immunopharmacology. 2020;85:106615.
doi:10.1016/j.intimp.2020.106615 .

Ferizović, Harisa, Spasojević, Nataša, Stefanović, Bojana, Janković, Milica, Dronjak, Slađana, "The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats" in International Immunopharmacology, 85 (2020):106615,
https://doi.org/10.1016/j.intimp.2020.106615 . .

TY  - CONF
AU  - Ferizović, Harisa
AU  - Spasojević, Nataša
AU  - Stefanović, Bojana
AU  - Dronjak, Slađana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12813
AB  - Disrupted circadian rhythm and sleep disorders are one of the crucial symptoms of major depressive disorder. While physiological role of melatonin and its antioxidative properties are well known, increasing number of studies show that melatonin may also exhibit antidepressive effects. Aim of our research was to examine effects of melatonin on catecholamine turnover and receptors in prefrontal cortex (PFC) of rats exposed to the chronic mild unpredictable stress (CUMS) model of depression. Two months old Wistar rats were subjected to the 4 weeks of CUMS. Both control animals and animals exposed to the CUMS were treated with either melatonin (10 mg/kg, i.p.) or vehicle. Levels of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), α1- and β2-adrenergic receptors in PFC were examined using Western blot procedure. Catecholamine synthesis through TH and DBH in PFC was not affected either by CUMS procedure or by melatonin treatment. However, animals exposed to the CUMS shoved elevated levels of COMT and decreased levels of α1- and β2-adrenergic receptors in PFC. Melatonin treatment improved levels of adrenergic receptors and decreased levels of COMT protein to the levels comparable with control animals. These findings show that melatonin treatment had protective role on PFC in chronic stress. Our results suggest that some of the melatonin effects were achieved through regulation of COMT and α1- and β2-adrenergic receptors protein levels. These preliminary results support potential therapeutic use of melatonin in treatment of depressive disorders.
PB  - Beograd : Srpsko farmakološko društvo (SFD)
C3  - 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem : Zbornik kratkih sadržaja radova
T1  - Efekat tretmana melatoninom na sintezu I degradaciju kateholamina i α1- i β2-adrenergičke receptore u prefrontalnoj kori pacova izloženih hroničnom blagom nepredvidivom stresu
T1  - Effects of melatonin treatment on catecholamine synthesis, degradation and α1-and β2-adrenergic receptors in prefrontal cortex of rats exposed to the chronic mild unpredictable stress
SP  - 206
EP  - 207
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12813
ER  - 

@conference{
author = "Ferizović, Harisa and Spasojević, Nataša and Stefanović, Bojana and Dronjak, Slađana",
year = "2019",
abstract = "Disrupted circadian rhythm and sleep disorders are one of the crucial symptoms of major depressive disorder. While physiological role of melatonin and its antioxidative properties are well known, increasing number of studies show that melatonin may also exhibit antidepressive effects. Aim of our research was to examine effects of melatonin on catecholamine turnover and receptors in prefrontal cortex (PFC) of rats exposed to the chronic mild unpredictable stress (CUMS) model of depression. Two months old Wistar rats were subjected to the 4 weeks of CUMS. Both control animals and animals exposed to the CUMS were treated with either melatonin (10 mg/kg, i.p.) or vehicle. Levels of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), α1- and β2-adrenergic receptors in PFC were examined using Western blot procedure. Catecholamine synthesis through TH and DBH in PFC was not affected either by CUMS procedure or by melatonin treatment. However, animals exposed to the CUMS shoved elevated levels of COMT and decreased levels of α1- and β2-adrenergic receptors in PFC. Melatonin treatment improved levels of adrenergic receptors and decreased levels of COMT protein to the levels comparable with control animals. These findings show that melatonin treatment had protective role on PFC in chronic stress. Our results suggest that some of the melatonin effects were achieved through regulation of COMT and α1- and β2-adrenergic receptors protein levels. These preliminary results support potential therapeutic use of melatonin in treatment of depressive disorders.",
publisher = "Beograd : Srpsko farmakološko društvo (SFD)",
journal = "14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem : Zbornik kratkih sadržaja radova",
title = "Efekat tretmana melatoninom na sintezu I degradaciju kateholamina i α1- i β2-adrenergičke receptore u prefrontalnoj kori pacova izloženih hroničnom blagom nepredvidivom stresu, Effects of melatonin treatment on catecholamine synthesis, degradation and α1-and β2-adrenergic receptors in prefrontal cortex of rats exposed to the chronic mild unpredictable stress",
pages = "206-207",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12813"
}

Ferizović, H., Spasojević, N., Stefanović, B.,& Dronjak, S.. (2019). Efekat tretmana melatoninom na sintezu I degradaciju kateholamina i α1- i β2-adrenergičke receptore u prefrontalnoj kori pacova izloženih hroničnom blagom nepredvidivom stresu. in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem : Zbornik kratkih sadržaja radova
Beograd : Srpsko farmakološko društvo (SFD)., 206-207.
https://hdl.handle.net/21.15107/rcub_vinar_12813

Ferizović H, Spasojević N, Stefanović B, Dronjak S. Efekat tretmana melatoninom na sintezu I degradaciju kateholamina i α1- i β2-adrenergičke receptore u prefrontalnoj kori pacova izloženih hroničnom blagom nepredvidivom stresu. in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem : Zbornik kratkih sadržaja radova. 2019;:206-207.
https://hdl.handle.net/21.15107/rcub_vinar_12813 .

Ferizović, Harisa, Spasojević, Nataša, Stefanović, Bojana, Dronjak, Slađana, "Efekat tretmana melatoninom na sintezu I degradaciju kateholamina i α1- i β2-adrenergičke receptore u prefrontalnoj kori pacova izloženih hroničnom blagom nepredvidivom stresu" in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem : Zbornik kratkih sadržaja radova (2019):206-207,
https://hdl.handle.net/21.15107/rcub_vinar_12813 .

TY  - JOUR
AU  - Stefanović, Bojana
AU  - Spasojević, Nataša
AU  - Jovanović, Predrag
AU  - Ferizović, Harisa
AU  - Dronjak, Slađana
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7795
AB  - OBJECTIVE: This study investigated the effects of chronic melatonin treatment on gene expression of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus of rats subjected to chronic unpredictable mild stress (CUMS). BACKGROUND: Preclinical studies have also shown that melatonin prevented short- and long-term memory impairments and exhibited antidepressant-like actions. METHODS: For this study, we used 24 animals, which were divided into four groups, and the experiment lasted 4 weeks. We quantifi ed the changes in mRNA and protein levels of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus after melatonin treatment. RESULTS: Our results demonstrated a decreased gene expression of α1-, α2- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress, while there was no change in gene expression of β1-adrenoceptors. Melatonin treatment in the CUMS rats prevented the stress-induced decrease in mRNA and protein levels of α1-and β2-adrenoceptors, whereas did not affect either on mRNA or protein level of β1-and α2-adrenoceptors. CONCLUSION: Our data suggest that melatonin, by increasing reduced levels of α1- and β2-adrenoceptors mRNA and protein in the hippocampus of chronic stressed rats, may be benefi cial in conditions such as chronic stress and provides an experimental opportunity to probe into further molecular mechanisms underlying the regulation of these receptor subtype.
T2  - Bratislava Medical Journal
T1  - Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress
VL  - 119
IS  - 7
SP  - 429
EP  - 433
DO  - 10.4149/BLL_2018_078
ER  - 

@article{
author = "Stefanović, Bojana and Spasojević, Nataša and Jovanović, Predrag and Ferizović, Harisa and Dronjak, Slađana",
year = "2018",
abstract = "OBJECTIVE: This study investigated the effects of chronic melatonin treatment on gene expression of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus of rats subjected to chronic unpredictable mild stress (CUMS). BACKGROUND: Preclinical studies have also shown that melatonin prevented short- and long-term memory impairments and exhibited antidepressant-like actions. METHODS: For this study, we used 24 animals, which were divided into four groups, and the experiment lasted 4 weeks. We quantifi ed the changes in mRNA and protein levels of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus after melatonin treatment. RESULTS: Our results demonstrated a decreased gene expression of α1-, α2- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress, while there was no change in gene expression of β1-adrenoceptors. Melatonin treatment in the CUMS rats prevented the stress-induced decrease in mRNA and protein levels of α1-and β2-adrenoceptors, whereas did not affect either on mRNA or protein level of β1-and α2-adrenoceptors. CONCLUSION: Our data suggest that melatonin, by increasing reduced levels of α1- and β2-adrenoceptors mRNA and protein in the hippocampus of chronic stressed rats, may be benefi cial in conditions such as chronic stress and provides an experimental opportunity to probe into further molecular mechanisms underlying the regulation of these receptor subtype.",
journal = "Bratislava Medical Journal",
title = "Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress",
volume = "119",
number = "7",
pages = "429-433",
doi = "10.4149/BLL_2018_078"
}

Stefanović, B., Spasojević, N., Jovanović, P., Ferizović, H.,& Dronjak, S.. (2018). Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress. in Bratislava Medical Journal, 119(7), 429-433.
https://doi.org/10.4149/BLL_2018_078

Stefanović B, Spasojević N, Jovanović P, Ferizović H, Dronjak S. Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress. in Bratislava Medical Journal. 2018;119(7):429-433.
doi:10.4149/BLL_2018_078 .

Stefanović, Bojana, Spasojević, Nataša, Jovanović, Predrag, Ferizović, Harisa, Dronjak, Slađana, "Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress" in Bratislava Medical Journal, 119, no. 7 (2018):429-433,
https://doi.org/10.4149/BLL_2018_078 . .