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Article ; Online: Sleep disturbances and depression

Grubač Željko / Jovanović Đurđa / Puškaš Nela / Hrnčić Dragan

Medicinski Podmladak, Vol 69, Iss 3, Pp 48-

Directions and mechanisms of interaction

2018 Volume 55

Abstract: Sleep represents physiological process which effects are crucial to maintain homeostasis. Sleep disturbances are widely spread within the population worldwide. The loss in quantity or quality of sleep is associated with numerous diseases. Also, sleep ... ...

Abstract	Sleep represents physiological process which effects are crucial to maintain homeostasis. Sleep disturbances are widely spread within the population worldwide. The loss in quantity or quality of sleep is associated with numerous diseases. Also, sleep disturbances are highly connected to depressive disorders, but exact mechanism of this interaction still remains unknown. Understanding the underlying mechanisms could be the key for treatment of both disorders especially in patients with psychosomatic and psychiatric comorbidities. Therefore, in this article, we will summarize the most recent findings on the connection between sleep disturbances and depressive disorders, including the mechanisms of this interaction.
Keywords	sleep ; depression ; sleep disturbances ; BDNF ; Medicine ; R
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	University of Belgrade, Medical Faculty
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The effects of hydrogen sulfide synthesis inhibition in lindane-induced seizures in rats

Šutulović Nikola / Rašić-Marković Aleksandra / Grubač Željko / Đurić Emilija / Hrnčić Dragan

Archives of Biological Sciences, Vol 72, Iss 4, Pp 457-

A behavioral and EEG study

2020 Volume 463

Abstract: Lindane-induced seizure in rats is a model of refractory generalized epilepsy. Hydrogen sulfide (H2S) is a gasotransmitter with different physiological and pathological roles. Cystathionine-β-synthase (CBS) is a major enzyme responsible for H2S ... ...

Abstract	Lindane-induced seizure in rats is a model of refractory generalized epilepsy. Hydrogen sulfide (H2S) is a gasotransmitter with different physiological and pathological roles. Cystathionine-β-synthase (CBS) is a major enzyme responsible for H2S production in the brain. The aim of this study was to investigate the effects of H2S production inhibition using aminooxyacetate (a CBS inhibitor) on behavioral and EEG manifestations of lindane-induced seizures. Male Wistar rats with previously implanted EEG electrodes were intraperitoneally (i.p.) treated with 4 mg/kg lindane and observed for convulsive behavior and EEG manifestations during the next 30 min. Aminooxyacetate (5, 15 and 25 mg/kg, i.p.) or saline, was injected 30 min prior to lindane. Convulsive behavior was assessed by seizure incidence, latency time and severity (grades 0-4). The number and duration of ictal periods in the EEG were also analyzed. Seizure incidence was higher in rats treated with aminooxyacetate (AOA) before lindane, but not significantly when compared with those treated only with lindane. However, AOA significantly decreased the latency time and augmented the severity of lindane-induced seizures in a dose-dependent manner. EEG analysis revealed an increased number and duration of ictal periods in rats receiving AOA prior to lindane. H2S production inhibition aggravated lindane-induced seizures, which showed a functional relationship between H2S and the effects of lindane.
Keywords	aminooxyacetate ; cystathionine-β-synthase ; eeg ; hydrogen sulfide ; lindane ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	University of Belgrade, University of Novi Sad
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Behavioral alterations in open field test in an experimental model of prostatitis

Zubelić Aleksa / Knežević Božo / Grubač Željko / Šutulović Nikola / Stanojlović Olivera / Hrnčić Dragan

Medicinski Podmladak, Vol 70, Iss 4, Pp 34-

2019 Volume 40

Abstract: Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of genitourinary system in male population. It is frequently accompanied by psychosocial disorders which include anxiety. Despite numerous ... ...

Abstract	Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of genitourinary system in male population. It is frequently accompanied by psychosocial disorders which include anxiety. Despite numerous clinical studies, the mechanisms of this link are still unclear, partly due to the lack of studies on experimental animal models. Aim: The aim of this study was to examine locomotion activity and anxiety in rats, with experimentally induced CP/CPPS, using the open field test. Material and methods: Wistar male rats were randomly distributed into control and experimental group. In experimental group, CP/CPPS was induced by single intraprostatic injection of 3% l-carrageenan. Development of pelvic pain syndrome was assessed by evaluating mechanical pain thresholds by electronic von Frey aesthesiometer (eVF). The rats were individually tested in the open field, seventh day following the intraprostatic injection. Results: In animals from the experimental group, distance and time of ambulatory movement in the open field test were significantly decreased, number of rearing reduced, time spent in the center of the open field significantly decreased, while index of thigmotaxis was significantly increased compared to the control animals. Conclusion: Results of this study indicate anxiogenic effect of CP/CPPS in rats.
Keywords	chronic prostatitis ; chronic pelvic pain syndrome ; open field test ; anxiety ; rats ; Medicine ; R
Subject code	796
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	University of Belgrade, Medical Faculty
Document type	Article ; Online
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Article ; Online: Chronic Prostatitis/Chronic Pelvic Pain Syndrome Induces Depression-Like Behavior and Learning-Memory Impairment: A Possible Link with Decreased Hippocampal Neurogenesis and Astrocyte Activation.

Šutulović, Nikola / Vesković, Milena / Puškaš, Nela / Zubelić, Aleksa / Jerotić, Djurdja / Šuvakov, Sonja / Despotović, Sanja / Grubač, Željko / Mladenović, Dušan / Macut, Djuro / Rašić-Marković, Aleksandra / Simić, Tatjana / Stanojlović, Olivera / Hrnčić, Dragan

Oxidative medicine and cellular longevity

2023 Volume 2023, Page(s) 3199988

Abstract: Pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains unclear since it represents an interplay between immunological, endocrine, and neuropsychiatric factors. Patients suffering from CP/CPPS often develop mental health- ... ...

Abstract	Pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains unclear since it represents an interplay between immunological, endocrine, and neuropsychiatric factors. Patients suffering from CP/CPPS often develop mental health-related disorders such as anxiety, depression, or cognitive impairment. The aim of this study was to investigate depression-like behavior, learning, and memory processes in a rat model of CP/CPPS and to determine the alterations in hippocampal structure and function. Adult male Wistar albino rats (
MeSH term(s)	Humans ; Animals ; Rats ; Male ; Prostatitis/complications ; Prostatitis/metabolism ; Astrocytes/metabolism ; Chronic Disease ; Depression/complications ; Neuroinflammatory Diseases ; Rats, Wistar ; Pelvic Pain ; Hippocampus/metabolism ; Neurogenesis
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2455981-7
ISSN	1942-0994 ; 1942-0994
ISSN (online)	1942-0994
ISSN	1942-0994
DOI	10.1155/2023/3199988
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The central nervous system is not imunoprivileged

Hrnčić Dragan / Šutulović Nikola / Grubač Željko / Rašić-Marković Aleksandra / Stanojlović Olivera

Vojnosanitetski Pregled, Vol 75, Iss 8, Pp 820-

Inflammation and epileptogenesis

2018 Volume 825

Abstract: ... ...

Abstract	nema
Keywords	central nervous system ; epilepsy ; inflammation ; oxidative stress ; Medicine (General) ; R5-920
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Military Health Department, Ministry of Defance, Serbia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modulatory effects of delta sleep-inducing peptide in a lindane model of generalized seizures

Hrnčić Dragan / Grubač Željko / Šutulović Nikola / Rašić-Marković Aleksandra / Ademović Anida / Stanojlović Olivera

Archives of Biological Sciences, Vol 70, Iss 3, Pp 559-

2018 Volume 566

Abstract: Delta sleep-inducing peptide (DSIP) is an endogenous peptide that is constantly present in several different brain regions. Lindane is used as a pesticide and scabicide, but it also induces seizures refractory to conventional antiepileptics. The aim of ... ...

Abstract	Delta sleep-inducing peptide (DSIP) is an endogenous peptide that is constantly present in several different brain regions. Lindane is used as a pesticide and scabicide, but it also induces seizures refractory to conventional antiepileptics. The aim of this paper was to determine whether DSIP modulates lindane-induced seizures in rats in a behavioral and electroencephalographic (EEG) study. DSIP (1 mg/kg, i.p.) or dimethyl-sulfoxide (DMSO, 0.5 ml/kg, intraperitoneally (i.p.)) were injected 30 min before lindane (8 mg/kg, i.p.) to adult male rats with previously implanted electrodes for EEG registration. During the following 30 min, the EEG was registered, and the following behavioral characteristics of seizures were observed: incidence, latency and intensity. A descriptive scale with grades from 0 to 4 provided an estimate of seizure intensity. In the EEG, the number and duration of ictal periods were analyzed using NeuroSciLaBG (Belgrade, Serbia) software. The lethality rate was also analyzed. DSIP-treated animals showed significantly modified characteristics of lindane-induced seizures when compared to the group without DSIP pretreatment (i.e. a reduced seizure intensity and a prolonged seizure latency period). However, no significant effects of DSIP on seizure incidence and lindane-induced lethality were observed. EEG analyses showed a significantly decreased number of lindane-induced EEG ictal periods in DSIP-treated animals, but with unaltered duration. These results show that DSIP favorably modulates lindane-induced seizures in rats, showing a potential to be an adjuvant component of antiepileptic treatment strategy for refractory seizures. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175032]
Keywords	behavior ; delta sleep-inducing peptide (DSIP) ; EEG ; epilepsy ; refractory seizures lindane ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	University of Belgrade, University of Novi Sad
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Experimental chronic sleep fragmentation alters seizure susceptibility and brain levels of interleukins 1β and 6.

Grubač, Željko / Šutulović, Nikola / Jerotić, Djudja / Šuvakov, Sonja / Rašić-Marković, Aleksandra / Macut, Djuro / Simić, Tatjana / Stanojlović, Olivera / Hrnčić, Dragan

Acta neurobiologiae experimentalis

2021 Volume 81, Issue 1, Page(s) 96–109

Abstract: Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of ... ...

Abstract	Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of chronic sleep fragmentation on seizure susceptibility and brain cytokine profile. Chronic sleep fragmentation in male rats with implanted EEG electrodes was achieved by the treadmill method. Rats were randomized to: treadmill control (TC); activity control (AC) and sleep fragmentation (SF) group. Convulsive behavior was assessed 14 days later by seizure incidence, latency time and seizure severity during 30 min following lindane administration. The number and duration of EEG ictal periods were determined. Levels of IL-1β and IL-6 were measured in the animals' serum and brain structures (hippocampus, thalamus and cerebral cortex), in separate rat cohort that underwent the same fragmentation protocol except lindane administration. Incidence and severity of seizures were significantly increased, while latency was significantly decreased in SF+L compared with TC+L group. Seizure latency was also significantly decreased in SF+L compared to AC+L group. The number and duration of ictal periods were increased in the SF+L compared to the AC+L group. IL-1β was significantly increased in the thalamus, cortex and hippocampus in the SF compared to the AC and TC groups. IL-6 was statistically higher only in the cortex of SF animals, while in the thalamic or hippocampal tissue, no difference was observed between the groups. It could be concluded that fourteen-day sleep fragmentation increases seizure susceptibility in rats and modulates brain production of IL-1β and IL-6. Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of chronic sleep fragmentation on seizure susceptibility and brain cytokine profile. Chronic sleep fragmentation in male rats with implanted EEG electrodes was achieved by the treadmill method. Rats were randomized to: treadmill control (TC); activity control (AC) and sleep fragmentation (SF) group. Convulsive behavior was assessed 14 days later by seizure incidence, latency time and seizure severity during 30 min following lindane administration. The number and duration of EEG ictal periods were determined. Levels of IL-1β and IL-6 were measured in the animals’ serum and brain structures (hippocampus, thalamus and cerebral cortex), in separate rat cohort that underwent the same fragmentation protocol except lindane administration. Incidence and severity of seizures were significantly increased, while latency was significantly decreased in SF+L compared with TC+L group. Seizure latency was also significantly decreased in SF+L compared to AC+L group. The number and duration of ictal periods were increased in the SF+L compared to the AC+L group. IL-1β was significantly increased in the thalamus, cortex and hippocampus in the SF compared to the AC and TC groups. IL-6 was statistically higher only in the cortex of SF animals, while in the thalamic or hippocampal tissue, no difference was observed between the groups. It could be concluded that fourteen-day sleep fragmentation increases seizure susceptibility in rats and modulates brain production of IL-1β and IL-6.
MeSH term(s)	Animals ; Brain/metabolism ; Cerebral Cortex/physiopathology ; Disease Models, Animal ; Electroencephalography/methods ; Hippocampus/physiopathology ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Male ; Rats ; Seizures/complications ; Seizures/metabolism ; Seizures/physiopathology ; Sleep Deprivation/complications ; Sleep Deprivation/physiopathology
Chemical Substances	Interleukin-1beta ; Interleukin-6
Language	English
Publishing date	2021-06-23
Publishing country	Poland
Document type	Journal Article
ZDB-ID	184409-x
ISSN	1689-0035 ; 0065-1400
ISSN (online)	1689-0035
ISSN	0065-1400
DOI	10.21307/ane-2021-010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Folic acid supplementation alleviates behavioral manifestations of lindane-induced seizures

Đurić Emilija / Hrnčić Dragan / Šutulović Nikola / Škrijelj Daniel / Grubač Željko / Ćirković Valentina / Rašić-Marković Aleksandra / Stanojlović Olivera

Archives of Biological Sciences, Vol 71, Iss 3, Pp 403-

2019 Volume 408

Abstract: Lindane is a scabicide and pesticide that can exert neurotoxic effects such as tonic and clonic seizures that are refractory to many antiepileptic drugs. Folic acid stands out as a potential substance worth testing for its neuroprotective and in certain ... ...

Abstract	Lindane is a scabicide and pesticide that can exert neurotoxic effects such as tonic and clonic seizures that are refractory to many antiepileptic drugs. Folic acid stands out as a potential substance worth testing for its neuroprotective and in certain experimental models anticonvulsive effects. The aim of the present study was to examine the potential therapeutic value of folic acid supplementation on the behavioral characteristics of lindane-induced seizures. Adult male Wistar rats were divided into the following groups: Controls: dimethyl sulfoxide-injected (C1), saline-treated (C2); lindane (4 mg/ kg; 6 mg/kg; 8 mg/kg; L4; L6; L8, respectively); folic acid 15 mg/kg (F) and F administered 30 min prior to L4, L6, or L8 (L4F; L6F; L8F, respectively). Convulsive behavior was assessed by the incidence of seizures, seizure latency and seizure severity. Lindane administration has shown a tendency of proportional increase in seizure incidence, decrease in seizure latency and increase in seizure intensity. Pretreatment with folic acid significantly prolonged the latency period and decreased the frequency of grade 4 seizures in the L8F group when compared to the L8 group. We concluded that folic acid alleviates the behavioral manifestations of lindane-induced seizures and that it can be applied as a potential adjuvant in lindane-poisoned patients; however, further research is still needed. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175032]
Keywords	lindane ; folic acid ; seizures ; rat ; intoxication ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	University of Belgrade, University of Novi Sad
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exploratory behavior alteration as an epileptic comorbidity in elevated plus maze test

Ademović Anida / Leković Aleksa / Knežević Božo / Grubač Željko / Šutulović Nikola / Hrnčić Dragan / Stanojlović Olivera

Medicinski Podmladak, Vol 68, Iss 3, Pp 22-

2017 Volume 28

Abstract: Introduction: Epileptic seizure consists of preictal, ictal and postictal period. Postictal period is characterized by a variety of psychiatric phenomenon of which the most frequent ones are anxiety and depressive disorder. Anxiety in rodents can be ... ...

Abstract	Introduction: Epileptic seizure consists of preictal, ictal and postictal period. Postictal period is characterized by a variety of psychiatric phenomenon of which the most frequent ones are anxiety and depressive disorder. Anxiety in rodents can be assessed by measuring the exploratory behavior. Lindane evokes generalized tonic-clonic epileptic seizures in rats, when applied intraperitoneally, due to its lypophilic characteristics. Aim: The aim of this study was to assess exploratory behavior linked with anxiety level in the elevated plus maze test (EPM) upon generalized seizures, induced by lindane in male rats. Material and methods: The experiment was conducted on Wistar albino male rats that were randomly divided into: control group (DMSO, 0.5 ml/kg) and experimental group (lindane, 8 mg/kg) (n=8, each). After the drug injection, the assessment of the seizure intensity lasted for 30 minutes. Descriptive rating scale was used to describe the seizure severity. Subsequently, the EPM testing took place immediately after evoking the seizure (Test 1), after 1h (Test 2) and after 24h (Test 3). Time spent in open areas and number of transitions was further analyzed. Results: Experimental group of animals spent less time in open areas of EPM, when compared to controls in Test 1 and Test 2. The same holds true for the number of transitions to the open area, i.e. lindane-treated animals tend to stay in enclosed parts of the maze in Test1, Test 2. Finally, in Test 3 there was no significant difference between the groups, in any parameter of interest. Conclusion: Lindane-induced generalized epileptic seizures are accompanied by reduced exploratory behavior in the elevated plus maze test, up to 24h after the seizure ended. This finding can be a basis for the further translational research of anxiety as epileptic comorbidity in this experimental model of epilepsy.
Keywords	anxiety-related behavior ; elevated plus maze ; lindane ; rats ; Medicine ; R
Subject code	150
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	University of Belgrade, Medical Faculty
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Basic characteristics of epileptiform discharges triggered by lindane in rats

Useinović Nemanja / Vorkapić Marko / Leković Aleksa / Ademovič Anida / Šutulović Nikola / Grubač Željko / Rašić-Marković Aleksandra / Hrnčić Dragan / Stanojlović Olivera

Medicinski Podmladak, Vol 69, Iss 3, Pp 69-

2018 Volume 75

Abstract: Introduction: EEG is a widely used method of epilepsy examination. In order to quantitatively inspect ictal EEG findings, a number of mathematical models have been developed over the years, one of them being the Fast Fourier Transform (FFT). It ... ...

Abstract	Introduction: EEG is a widely used method of epilepsy examination. In order to quantitatively inspect ictal EEG findings, a number of mathematical models have been developed over the years, one of them being the Fast Fourier Transform (FFT). It transforms the signal from time domain into frequency domain, giving information about their power spectral densities (PSD). Lindane is a well-established neurotoxic agent often used in experimental studies as a model of generalized epilepsy. This study aims to quantitatively examine the characteristics of ictal EEG activity in rats on model of generalized epilepsy induced by lindane. Materials and Methods: Wistar albino rats were used for the study. Electrodes were surgically implanted over the frontal, parietal and occipital cortices of each animal for EEG recording purposes prior to lindane administration in convulsive dose. An 8-channel EEG apparatus was used, combined with a software developed in the Laboratory (NeuroSciLaBG). Ictal EEG epochs were extracted from the original signal and FFT analysis performed to obtain information considering PSD in predefined frequency bands. Amplitude histogram feature of the software was used to differentiate ictal spikes based on their voltage. Results: FFT analysis has yielded important information regarding spectral powers in frequency domain. Ictal EEG showed considerable stratification, theta frequency band (4-7 Hz) being markedly dominant. Amplitude histogram showed the majority of spikes to be in the voltage ranges up to 250 μV, while higher voltage spikes were rarely observed. Conclusion: FFT is capable of giving important information about ictal period characteristics. Ictal periods induced by lindane are characterized by dominancy of theta rhythm and spiking activity mostly in amplitude bins up to 250 μV. FFT and amplitude histograms can be of critical importance in the future pharmacological and toxicity studies.
Keywords	seizures ; EEG ; FFT ; lindane ; rats ; Medicine ; R
Subject code	621
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	University of Belgrade, Medical Faculty
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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