Aleksandra Rašić-marković - Academia.edu (original) (raw)

Papers by Aleksandra Rašić-marković

Archives of Gerontology and Geriatrics, 2002

Medicinska istraživanja, 2022

Stress is present in our everyday lives and it is considered to be the driving force of evolution... more Stress is present in our everyday lives and it is considered to be the driving force of evolution. Anxiety, chronic worries and panic attacks are the most common consequences of long-term and exhausting stress. The most significant fundamental contribution that is crucial for the development of the modern concept of stress was made by Claude Bernard who proposed the theory that the body was constantly maintaining a stable and well-balanced internal environment or "milieu interieur". Maintaining the internal environment constant was defined as homeostasis by Cannon who proposed two maintenance mechanisms-through negative feedback from the autonomic nervous system and through sensory organs. Hans Selye proposed stress as non-specific strain on the body, caused by an altered body function which is followed by the release of stress hormones. He named this process the general adaptation syndrome which had three stages: alarm reaction, initial phase exhibiting "fight or flight" response; resistance, when body is getting used to being stressed, and exhaustion, when resistance to stress is gradually decreased and collapses. Hans Selye was the first to coin the term "heterostasis" representing the procedure by which a new stable state was achieved by the activation of physiological adaptive mechanisms. Lazarus highlighted emotions as an important factor in behavior in response to stress and provided a description of various reactions to stressors. He emphasized the process of cognitive assessment as a mediator in dealing with stressors-how a person imagines or evaluates an event in order to understand stress reactions in people. Eustress, considered to be positive stress leads to toned emotions, motivation and focused energy, while distress, negative stress, occurs after prolonged stress that exceeds our ability to deal with it. Distress causes anxiety or withdrawal (depression and anxiety), and is accompanied by unpleasant feelings and reduced work ability leading to mental and physical illnesses.

Neurotoxicity Research, Mar 7, 2016

Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE... more Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE). Finasteride, inhibitor of neurosteroid synthesis, may improve the course of HE. The aim of our study was to investigate the influence of finasteride on mean and relative power density of EEG bands, determined by spectral analysis, in rat model of thioacetamide-induced HE. Male Wistar rats were divided into groups: (1) control; (2) thioacetamide-treated group, TAA (900 mg/kg); (3) finasteride-treated group, FIN (150 mg/kg); and (4) group treated with finasteride (150 mg/kg) and thioacetamide (900 mg/kg), FIN + TAA. Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered during 3 subsequent days, and in FIN + TAA group FIN was administered 2 h before every dose of TAA. EEG was recorded 22–24 h after treatment and analyzed by fast Fourier transformation. While TAA did not induce significant changes in the beta band, mean and relative power in this band were significantly higher in FIN + TAA versus control group (p < 0.01). TAA caused a significant decline in mean power in alpha, theta, and delta band, and in FIN + TAA group the mean power in these bands was significantly higher compared with control. While in TAA group relative power was significantly decreased in theta (p < 0.01) and increased in delta band (p < 0.01) versus control, the opposite changes were found in FIN + TAA group: an increase in theta (p < 0.01) and a decrease in delta relative power (p < 0.01). In this study, finasteride pretreatment caused EEG changes that correspond to mild TAA-induced HE.

Oxidative Medicine and Cellular Longevity, Aug 21, 2021

Sleep architecture alterations, among which sleep fragmentation is highly prevalent, represent ri... more Sleep architecture alterations, among which sleep fragmentation is highly prevalent, represent risk factors for a variety of diseases, ranging from cardiovascular to brain disorders, including anxiety. What mediates anxiety occurrence upon sleep fragmentation is still a matter of debate. We hypothesized that the sleep fragmentation effects on anxiety are dependent on its duration and mediated by increased oxidative stress and alterations in the number of parvalbumin (PV+) interneurons in the hippocampus. Sleep was fragmented in rats by the treadmill method during a period of 14 days (SF group). Rats with undisturbed sleep in the treadmill (TC group) and those receiving equal amounts of treadmill belt motion (EC group) served as controls. To assess anxiety, we subjected rats to the open field, elevated plus maze, and light-dark tests on the 0, 7 th , and 14 th day. Upon the last test, brain structures were sampled for oxidative stress assessment and PV+ interneuron immunohistochemistry. The results of ethological tests of anxiety-linked behavior suggested duration-dependent anxiogenic potential of sleep fragmentation. Rats' anxiety-linked behavior upon sleep fragmentation significantly correlated with oxidative stress. The rats with fragmented sleep (SF) showed significantly higher oxidative stress in the hippocampus, thalamus, and cortex, compared to controls (TC and EC), while the antioxidant enzymes' activity was significantly decreased. No significant differences were observed in hippocampal PV+ interneurons among these groups. Our results showed that duration of sleep fragmentation is a significant determinant of anxiety-linked behavior, and these effects are mediated through oxidative distress in the brain. Herein, it is revealed that the sleep fragmentation-oxidative stress-anxiety axis contributes to our better understanding of pathophysiological processes, occurring due to disrupted sleep patterns.

Oxidative Medicine and Cellular Longevity, Mar 2, 2021

Mechanisms of the brain-related comorbidities in chronic prostatitis/chronic pelvic pain syndrome... more Mechanisms of the brain-related comorbidities in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still largely unknown, although CP/CPPS is one of the major urological problems in middle-aged men, while these neuropsychological incapacities considerably diminish life quality. The objectives of this study were to assess behavioral patterns in rats with CP/CPPS and to determine whether these patterns depend on alterations in the brain oxidative stress, corticosterone, and hippocampal parvalbumin-positive (PV+) interneurons. Adult male Wistar albino rats from CP/CPPS (intraprostatic injection of 3% λ-carrageenan, day 0) and sham (0.9% NaCl) groups were subjected to pain and anxiety-like behavior tests (days 2, 3, and 7). Afterwards, rats were sacrificed and biochemical and immunohistochemical analyses were performed. Scrotal allodynia and prostatitis were proven in CP/CPPS, but not in sham rats. Ethological tests (open field, elevated plus maze, and light/dark tests) revealed significantly increased anxiety-like behavior in rats with CP/CPPS comparing to their sham-operated mates starting from day 3, and there were significant intercorrelations among parameters of these tests. Increased oxidative stress in the hippocampus, thalamus, and cerebral cortex, as well as increased serum corticosterone levels and decreased number of hippocampal PV+ neurons, was shown in CP/CPPS rats, compared to sham rats. Increased anxiety-like behavior in CP/CPPS rats was significantly correlated with these brain biochemical and hippocampal immunohistochemical alterations. Therefore, the potential mechanisms of observed behavioral alterations in CP/CPPS rats could be the result of an interplay between increased brain oxidative stress, elevated serum corticosterone level, and loss of hippocampal PV+ interneurons.

Reviews in The Neurosciences, Feb 28, 2019

Methionine is an essential sulphur-containing amino acid involved in protein synthesis, regulatio... more Methionine is an essential sulphur-containing amino acid involved in protein synthesis, regulation of protein function and methylation reactions. Dietary methionine restriction (0.12-0.17% methionine in food) extends the life span of various animal species and delays the onset of agingassociated diseases and cancers. In the liver, methionine restriction attenuates steatosis and delays the development of non-alcoholic steatohepatitis due to antioxidative action and metabolic reprogramming. The limited intake of methionine stimulates the fatty acid oxidation in the liver and the export of lipoproteins as well as inhibits de novo lipogenesis. These effects are mediated by various signaling pathways and effector molecules, including sirtuins, growth hormone/ insulin-like growth factor-1 axis, sterol regulatory element binding proteins, adenosine monophosphate-dependent kinase and general control nonderepressible 2 pathway. Additionally, methionine restriction stimulates the synthesis of fibroblast growth factor-21 in the liver, which increases the insulin sensitivity of peripheral tissues. In the brain, methionine restriction delays the onset of neurodegenerative diseases and increases the resistance to various forms of stress through antioxidative effects and alterations in lipid composition. This review aimed to summarize the morphological, functional and molecular changes in the liver and brain caused by the methionine restriction, with possible implications in the prolongation of maximal life span.

Applied Physiology, Nutrition, and Metabolism, Mar 1, 2020

We compared the effects of aerobic high-intensity training (HIT) and isoinertial resistance train... more We compared the effects of aerobic high-intensity training (HIT) and isoinertial resistance training (IRT) on the strength, mass, architecture, intermuscular adipose tissue (IMAT) quality, and neuromuscular activation of the quadriceps in elderly subjects. Twelve healthy men (69.3 ± 4.2 years; 77.8 ± 10.4 kg; 1.72 ± 0.05 m) were exposed to 8 weeks of HIT (7 × 2-min cycling repetitions at 90% ofVO 2peak , 3 times/week) and, after 4 months (detraining), to IRT (4 × 7 maximal concentric-eccentric knee extensions, 3 times/week). Before and after trainings, we measured knee extension isometric (T MVC) and dynamic (T C) maximal concentric torque, anatomical cross-sectional area (ACSA) at 25, 50, and 75% of femur length, quadriceps volume (Vol), IMAT, pennation angle (θ p) of the fibers from the vastus lateralis, and voluntary activation (%Act). T MVC and T C were significantly larger only after IRT (P = 0.008); IRT was able to elicit a greater increase of ACSA than HIT; Vol increases similarly and significantly after HIT and IRT (P = 0.003-0.001); IMAT at 50% of femur length decreased after both HIT and IRT (P = 0.001-0.003); physiological cross-sectional area (PCSA) was larger after IRT than before (P = 0.025); specific torque did not change throughout the study (45.5 N cm −2 ± 12.0); %Act of the quadriceps was significantly affected only by IRT (P = 0.011). Both HIT and IRT are able to elicit beneficial modifications of muscular mass, architecture, and quality (reducing IMAT) in elderly subjects in connection with an amelioration of strength. HIT and IRT caused a homogeneous increase of ACSA and of Vol of the quadriceps. PCSA increases, but specific strength per unit of PCSA did not change. The increases of functional torque seemed to be attributed to a parallel increase of %Act and muscle hypertrophy only after IRT. Data suggest that IMAT may be a prominent indicator to track metabolic-dependent activity and skeletal muscle quality.

Acta Neurobiologiae Experimentalis, 2021

Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmen... more 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.

Medicinski Podmladak, 2022

Introduction: Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is the most commonly dia... more Introduction: Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is the most commonly diagnosed non-infectious prostatitis in urology. Studies have shown that CP/CPPS can induce neuroinflammation, which may result in CNS hyperexcitability and a tendency to develop epileptic seizures. Spike salvos are ictal EEG graph elements typical for the experimental model of lindane-induced seizures. There are a number of mathematical models for quantitative analysis of EEG, including the Fast Fourier Transform (FFT). It transforms the signal from time into the frequency domain, providing information on Power Spectral Densities (PSD). Aim: The aim of this study was to investigate the basic characteristics of epileptiform discharges induced by subconvulsive dose of lindane in rats, with experimentally induced CP/CPPS. Material and methods: CP/CPPS was induced by intraprostatic injection of 3% λ-carrageenan in male Wistar albino rats. Animals with CP/CPPS were implanted with EEG registration electrodes, and then administered lindane (4 mg/kg, i.p, experimental group, n = 6 per group) or its solvent (DMSO, control group, n = 6 per group). An 8-channel EEG device was used in combination with software developed in the laboratory (NeuroSciLaBG). Ictal EEG epochs were extracted from the original signal and FFT analysis was performed to obtain information taking into account PSD in predefined frequency bands. Results: There was no ictal activity in the EEG of control animals. In experimental animals, ictal activity occurred and the mean duration of the ictal period was 2.06 s. FFT analysis revealed that the alpha frequency range (7-15 Hz) was markedly dominant during ictal activity. Conclusion: The results of this study showed the characteristics of epileptiform discharges in animals with experimentally induced CP/CPPS. This study and animal model are suitable for future translational studies of the comorbidities of this syndrome.

Medicinski Podmladak, 2018

During the process of evolution, human brain has developed an extraordinary characteristic of neu... more During the process of evolution, human brain has developed an extraordinary characteristic of neuroplasticity, which is the capacity to change its structure and function under the influence of the external environment and experience. Numerous studies and evidence suggest beneficial effects of exercise on the brain and mental health. It is considered that exercise leads to the improvement of cognitive functions, with a particular emphasis on learning and memory. It was also found that exercise reduces the risk of developing dementia, it manifests an antidepressant effect and deflects cognitive decay in aging. This positive outcome is reflected in neurophysiological measures that showed increased prefrontal and temporal gray matter volume, decreased latency and increased amplitude of event related potentials in physically active individuals compared to sedentary controls. Even though the idea of the beneficial effects on mental health has been present for centuries, only recent studies have identified possible mechanisms that produce a synergistic positive effect. Potential neural mechanism that has been singled out is increased synthesis and release of neurotransmitters and neurotrophins, which then stimulate neurogenesis, angiogenesis and neuroplasticity. Exercise represents a potential adjuvant therapy in the treatment of neurodegenerative diseases, which not only reduces the cost of treatment, but also contributes to improving the quality of life and improving the mental health of an individual. It is therefore necessary to direct research into understanding the mechanisms by which exercise affects the brain.

Medicinal Chemistry, 2012

Previous work showed that several relatively speci®c inhibitors of neuronal nitric oxide synthase... more Previous work showed that several relatively speci®c inhibitors of neuronal nitric oxide synthase (nNOS) produce protection against MPTP induced dopaminergic toxicity. We examined whether a highly speci®c novel inhibitor of nNOS, ARR1 7338, could also protect against MPTP toxicity. ARR17338 produced dose-dependent signi®cant protection against MPTP induced depletion of dopamine and protected against MPTP induced depletions of tyrosine hydroxylase immunostained neurons in the substantia nigra. These results provide further evidence that inhibitors of nNOS may be useful for the treatment of Parkinson's disease. NeuroReport 11:1265±1268 & 2000 Lippincott Williams & Wilkins.

Archives of Biological Sciences, 2019

Lindane is a scabicide and pesticide that can exert neurotoxic effects such as tonic and clonic s... more 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 (C 1), saline-treated (C 2

Archives of Biological Sciences, 2018

effects of delta sleep-inducing peptide in a lindane model of generalized seizures.

Archives of Biological Sciences, 2020

Lindane-induced seizure in rats is a model of refractory generalized epilepsy. Hydrogen sulfide (... more Lindane-induced seizure in rats is a model of refractory generalized epilepsy. Hydrogen sulfide (H 2 S) is a gasotransmitter with different physiological and pathological roles. Cystathionine-β-synthase (CBS) is a major enzyme responsible for H 2 S production in the brain. The aim of this study was to investigate the effects of H 2 S 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. H 2 S production inhibition aggravated lindane-induced seizures, which showed a functional relationship between H 2 S and the effects of lindane.

Current Pharmaceutical Design, Feb 27, 2019

Physiology & Behavior, Mar 1, 2016

We investigated the effects of sleep disruption on seizure susceptibility of rats. • We used expe... more We investigated the effects of sleep disruption on seizure susceptibility of rats. • We used experimental model of lindane-induced refractory seizures. • Sleep disruption frequency resembled that in patients with severe sleep apnea. • Sleep disruption potentiated both behavioral and EEG epileptic activity in rat. • This could explain the occurrence of epileptic symptoms in sleep apnea patients.

Medicinska istraživanja, 2022

Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is a inflammatory syndr... more Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is a inflammatory syndrome, manifested by pain, voiding symptoms, sexual dysfunction, and mental health issues including anxiety. Beneficial effects of exercise are known, but its influence on CP/CPPS has not been investigated. This study aimed to determine the effects of chronic aerobic physical activity on anxiety-related behavior and pain in rats with experimental CP/CPPS. Material and Methods: Adult male Wistar albino rats (n=32) were randomly assigned to 4 groups (n=8 in each): Sham-SED (30-days sedentary-SED protocol on treadmill and intraprostatic injection of 0.9% NaCl); Sham-PA (30-days physically active-PA protocol on treadmill and intraprostatic injection of 0.9% NaCl); CP/CPPS-SED (30-days SED protocol on treadmill and intraprostatic injection of 3% λ-carrageenan); CP/CPPS-PA (30-days PA protocol on treadmill and intraprostatic injection of 3% λ-carrageenan). To establish pain dynamics, scrotal skin pain thresholds were measured by electronic von Frey aesthesiometer (evF) preoperatively: 2 and 1 day, and also postoperatively: 2 nd , 3 rd , and 7 th day. Anxiety-like behavior was estimated by subjectiong the animals to the open field (OF), elevated plus maze (EPM) and light/dark (L/D) tests at the same postoperative days as evF. Results: Rats that developed experimental CP/CPPS showed decreased mechanical pain threshold in the scrotal skin in all postoperative time points, in comparison to the Sham group. Also, in rats with prostatitis increased anxiety-like behavior was observed in OF, EMP and L/D test, compared to corresponding controls. Protocol of 30-day long exercise in rats with CP/CPPS led to reversion of anxiety-like behavior and increased scrotal pain threshold. Conclusion: Results of the present study showed that exercise pretreatment on the treadmill for 30 consecutive days led to the amelioration of anxiety-related and pain-related behavior in rats with CP/CPPS.

Hormones, Nov 12, 2018

Over the last decade, huge achievements have been made in the fields of neurophysiology, molecula... more Over the last decade, huge achievements have been made in the fields of neurophysiology, molecular endocrinology, and biochemistry, as well as in the successful translation of clinical research into diseases into clinical practice. As regards female reproduction, most of the advances made in this area were achieved in gonadal axis regulation, regulation of behavior through sex steroids, reproductive genetics, preservation of ovarian reproductive function, steroid profiling, and metabolic and overall reproductive outcomes. The coming years are expected to bring further understanding of the relationships between nutrition, energy metabolism, and reproductive function and to succeed in identifying new genetic markers linked to adverse metabolic and unfavorable cardiovascular outcomes in women. From our perspective, future research in the field of female reproduction should be directed toward doing research into genetic reproductive abnormalities and neuroendocrine diseases, pathophysiology, longterm health outcomes for oligo/amenorrhea, hyperandrogenism, and ovulatory dysfunction. It is additionally expected that a better understanding will be gained of the endocrinology of the placenta and of pregnancy, the role of the microbiome in female reproduction, the role of insulin sensitizers, anti-obesity and anti-diabetic drugs, and various advances in the prevention of ovarian damage caused by various oncology therapies, while new therapeutic options for the treatment of infertility, including kisspeptin, will be developed.

Medicinski podmladak

Archives of Gerontology and Geriatrics, 2002

Medicinska istraživanja, 2022

Neurotoxicity Research, Mar 7, 2016

Oxidative Medicine and Cellular Longevity, Aug 21, 2021

Oxidative Medicine and Cellular Longevity, Mar 2, 2021

Reviews in The Neurosciences, Feb 28, 2019

Applied Physiology, Nutrition, and Metabolism, Mar 1, 2020

Acta Neurobiologiae Experimentalis, 2021

Medicinski Podmladak, 2022

Medicinski Podmladak, 2018

Medicinal Chemistry, 2012

Archives of Biological Sciences, 2019

Archives of Biological Sciences, 2018

effects of delta sleep-inducing peptide in a lindane model of generalized seizures.

Archives of Biological Sciences, 2020

Current Pharmaceutical Design, Feb 27, 2019

Physiology & Behavior, Mar 1, 2016

Medicinska istraživanja, 2022

Hormones, Nov 12, 2018

Medicinski podmladak