scholarly journals Anxiogenic Potential of Experimental Sleep Fragmentation Is Duration-Dependent and Mediated via Oxidative Stress State

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Željko Grubač ◽  
Nikola Šutulović ◽  
Sonja Šuvakov ◽  
Djurdja Jerotić ◽  
Nela Puškaš ◽  
...  

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, 7th, and 14th 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.

2018 ◽  
Vol 16 (4) ◽  
pp. 45-48
Author(s):  
Platon P. Khokhlov ◽  
Ilia Yu. Tissen ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov ◽  
Petr D. Shabanov

The aim of this investigation was to reveal correlations between some behavioral patterns and orexin concentrations in the brain structures in rats after an acute psychoemotional stress. A group of rats was placed into a chamber with a tiger python for 25 mi nutes and then as a treatment these rats received orexin A or its antagonist SB-408124 administered intranasally for 7 days. Then the quantitive indexes of behavioral patterns in open field and elevated plus maze were registered. The orexin A level was investigated in the brain structures (amygdala, hippocampus, hypothalamus) of such rats by means of high-sensitive ELISA. The correlations were assessed with Spearman’s rank correlation test. As a result, a correlation between orexin A content in the amygdala and hypothalamus and a number of ambulations (line crossings) characterizing motor activity in open field test has been revealed. Therefore, the level of orexin A in the amygdala and hypothalamus demonstrates a direct and reverse link with locomotor activity of rats respectively. Also a correlation between orexin A level in the hippocampus and amygdala and the time of staying in the dark alleys of the elevated plus maze has been revealed. So, the content of orexin A in the hippocampus and amygdala reflects anxiety level of a rat. It is concluded there is a positive correlation between the orexin A content in the limbic structures of the brain and emotional behavior of rats.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0246184
Author(s):  
Roberta Cristina de França Silva ◽  
Mikaelle Albuquerque de Souza ◽  
Jaielison Yandro Pereira da Silva ◽  
Carolina da Silva Ponciano ◽  
Vanessa Bordin Viera ◽  
...  

Macaíba palm seed kernel is a source of lipids and phenolic compounds. The objective of this study was to evaluate the effects of macaíba palm seed kernel on anxiety, memory, and oxidative stress in the brain of health and dyslipidemic rats. Forty rats were used, divided into 4 groups (n = 10 each): control (CONT), dyslipidemic (DG), kernel (KG), and Dyslipidemic kernel (DKG). Dyslipidemia was induced using a high fat emulsion for 14 days before treatment. KG and DKG received 1000 mg/kg of macaíba palm seed kernel per gavage for 28 days. After treatment, anxiety tests were carried out using the Open Field Test (OFT), Elevated Plus Maze (EPM), and the Object Recognition Test (ORT) to assess memory. In the animals’ brain tissue, levels of malondialdehyde (MDA) and total glutathione (GSH) were quantified to determine oxidative stress. The data were treated with Two Way ANOVA followed by Tukey (p <0.05). Results demonstrated that the animals treated with kernel realized more rearing. DG and KG groomed less compared with CONT and DKG compared with all groups in OFT. KG spent more time in aversive open arms compared with CONT and DKG compared with all groups in EPM. Only DKG spent more time in the central area in EMP. KG and DKG showed a reduction in the exploration rate and MDA values (p <0.05). Data showed that macaíba palm seed kernel consumption induced anxiolytic-like behaviour and decreased lipids peroxidation in rats’ brains. On the other hand, this consumption by healthy and dyslipidemic animals compromises memory.


2011 ◽  
Vol 30 (2) ◽  
pp. 109-114 ◽  
Author(s):  
Alin Ciobica ◽  
Lucian Hritcu ◽  
Veronica Nastasa ◽  
Manuela Padurariu ◽  
Walther Bild

Inhibition of Central Angiotensin Converting Enzyme Exerts Anxiolytic Effects by Decreasing Brain Oxidative StressThis study investigated the effects of angiotensin II and captopril intracerebroventricular administration on anxiety status and brain oxidative stress. Elevated plus maze was used in order to asses the anxiety-like behavior, while the biochemical analysis included the determination of some antioxidant defense enzymes like superoxide dismutase and glutathione peroxidase and also a lipid peroxidation product (malondialdehyde). Our results provide additional evidence of angiotensin II induced anxiety-like effects and increased prooxidant status. Moreover, the blockade of angiotensin II, by the administration of an angiotensin converting enzyme inhibitor (captopril) resulted in anxiolytic effects and decreased oxidative stress status. In addition, we found a significant correlation between the time spent by rats in the open arms of the elevated plus maze and oxidative stress markers. This could raise important therapeutic issues regarding the anxiolytic effects of some angiotensin converting enzyme inhibitors used primarily for hypertension, such as captopril. Also, it seems that oxidative stress could play an important part in these actions.


2013 ◽  
Vol 8 (4) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Hikaru Kasuya ◽  
Erika Hata ◽  
Tadaaki Satou ◽  
Masaki Yoshikawa ◽  
Shinichiro Hayashi ◽  
...  

Various effects have been reported in the literature for the essential oil from Chamaecyparis obtusa (EOCO), such as antibacterial and antifungal activity. In this study, we examined the effect of EOCO on emotional behavior and stress-induced biomarkers. Male ICR mice, aged 5 weeks at the start of each experiment, were individually housed in cages for 1 week. After placing each mouse in a glass container and exposing it to EOCO for 90 min, we then investigated the influence on emotional behavior using the elevated-plus maze (EPM) test, which is one of the evaluation methods for anxiolytic-like behavior. Significant anxiolytic-like effects were observed for the 7.0 mg/L air EOCO ( P<0.05). After the EPM test, mice were dissected and changes in the stress-induced biomarkers within the brain were investigated by examining the amounts of fast nerve growth factor receptor (NGFR) and activity regulated cytoskeletal-associated protein (Arc) gene expression, and brain-derived neurotrophic factor (BDNF) and galactokinase 1 (GLK1) protein expression. Significant increases were observed in the amount of NGFR after inhalation of 7.0 mg/L air EOCO ( P<0.05). These results indicate that EOCO has both anxiolytic-like and stress mitigation effects.


Open Medicine ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Alin Ciobica ◽  
Veronica Bild ◽  
Lucian Hritcu ◽  
Manuela Padurariu ◽  
Walther Bild

AbstractIn addition to its known classical roles, the renin angiotensin system (RAS) has more subtle functions which include the regulation of emotional responses. Previous studies regarding the anxiety related behavior of RAS have showed controversial results. There is also evidence that oxidative stress accompanies angiotensin II infusion, but the role of AT1/AT2 specific receptors is not clear. The aim of this study was to evaluate the effects of central angiotensin II receptor blockers on anxiety state and oxidative stress. Behavioral testing included elevated plus maze, while oxidative stress status was measured though the extent of a lipid peroxidation product (malondialdehyde-MDA) and the specific activity of some defense antioxidant enzymes (superoxide dismutase-SOD and glutathione peroxidase-GPx). The rats treated with angiotensin II spent significantly less time in the open-arms of elevated-plus-maze, while the administration of losartan resulted in a significant increase of this time. We observed a significant increase of MDA concentration in the angiotensin II group and a decrease of MDA levels in both losartan and PD-123177 groups. In addition, a significant correlation was seen between the time spent in the open arms and oxidative stress markers. These findings could lead to important therapeutic aspects regarding the use of angiotensin II receptor blockers in anxiety-related disorders.


2016 ◽  
Vol 94 (9) ◽  
pp. 961-972 ◽  
Author(s):  
Ionut Caravan ◽  
Alexandra Sevastre Berghian ◽  
Remus Moldovan ◽  
Nicoleta Decea ◽  
Remus Orasan ◽  
...  

Menopause is accompanied by enhanced oxidative stress and behavioral changes, effects attenuated by antioxidants. The aim of this study was to evaluate the effects of caffeine on behavior and oxidative stress in an experimental model of menopause. Female rats were divided into the following groups: sham-operated (CON), sham-operated and caffeine-treated (CAF), ovariectomized (OVX), ovariectomized and caffeine-treated (OVX+CAF). Caffeine (6 mg/kg) and vehicle were administered for 21 days (subchronic) and 42 days (chronic), using 2 experimental subsets. Behavioral tests and oxidative stress parameters in the blood, whole brain, and hippocampus were assessed. The subchronic administration of caffeine decreased the lipid peroxidation and improved the antioxidant defense in the blood and brain. The GSH/GGSG ratio in the brain was improved by chronic administration, with reduced activities of antioxidant enzymes and enhanced nitric oxide and malondialdehyde levels. In particular, the lipid peroxidation in the hippocampus decreased in both experiments. The rats became hyperactive after 21 days of treatment, but no effect was observed after chronic administration. In both experimental subsets, caffeine had anxiolytic effects as tested in elevated plus maze. The administration of low doses of caffeine, for a short period of time, may be a new therapeutic approach to modulating the oxidative stress and anxiety in menopause.


Author(s):  
GHADA E. YASSIN ◽  
REHAM I. AMER ◽  
AHMED M. FAYEZ

Objective: Carbamazepine (CBZ) is used as a first line in the treatment of grand mal and partial seizures, but it suffers from many side effects on different systems of the body. The objective of the present study was optimization of CBZ vesicular structures using 23 multifactorial design for the most efficient targeting of CBZ to the brain via the intranasal route. Methods: The concentration of CBZ (10 and 20%), type of vesicles (niosomes and spanlastics) and speed of rotation (200 and 300 rpm) were considered as the independent variables XA, XB and XC respectively, while the dependent variables were particle size PS (Y1), polydispersity index PDI (Y2), zeta potential ZP (Y3) and entrapment efficiency EE (Y4). The study of the effect of different formulation variables was carried out using Design-Expert ® software. CBZ-loaded spanlastics and noisome were prepared by the ethanol injection method and thin film hydration method, respectively. The optimized formulation was subjected to viscosity measurement, in vitro drug release and physical stability studies. In vivo evaluations in rats for the optimized formulation in comparison to oral CBZ suspension was carried out using behavioral assessment by elevated plus maze test, determination of endothelial nitric oxide synthase (e-NOS), reduced glutathione (GSH) and ELISA estimation of TNFα. Results: The selected optimized formulation (F0) containing 20% CBZ and spanlastic vesicular structure showed PS, PDI, ZP, and the EE % of 350.09 nm, 0.830, 16.124mV and 82.777%, respectively. In vitro release study of F0 demonstrated the ability of the F0 to increase drug release in the range time from 10-60 min (p<0.05) when compared with CBZ suspension. The viscosity of F0 was nearly uniform (65 cps). The photomicrograph taken by the transmission electron microscopy (TEM) reveals the spherical shape of F0. Good physical stability for six months of storage at 25˚ C was found for F0. The optimized spanlastic formulation F0 showed a decrease in latency time in behavior assessment test using elevated plus Maze test, a decrease in serum eNOS and TNF-α and increase in GSH when compared with the oral CBZ suspension, in addition to the histopathological study that revealed the more CBZ uptake by the brain. Conclusion: The optimized spanlastic formulation F0 achieved better results when compared with the oral CBZ suspension for targeting the CBZ spanlastics vesicular structure to the brain via the nasal route.


2018 ◽  
Vol 9 (2) ◽  
pp. 1-8
Author(s):  
Amardeep Gautam ◽  
Rizwana Tabassum ◽  
Anju Katyal

Background: Hypobaric hypoxia refers to lower oxygen availability at high altitudes and is the cause of high altitude illness. Drugs such as acetazolamide and dexamethasone provide symptomatic relief and are associated with undesired side effects. Plant extracts such as Hypericum perforatum, which are documented to have neuromodulatory role can be more beneficial in ameliorating high altitude illness. Aims and Objective: Progressive cognitive decline is the hallmark characteristic of hypobaric hypoxia induced neuropathology attributed to ensuing oxidative stress and subsequent hippocampal damage. We have explored the efficacy of ethanolic extracts of Hypericum perforatum in amelioration of hypobaric hypoxia induced oxidative stress and associated behavioral deficits in mice.Material and Methods: Male Balb/c mice were exposed to simulated altitude of 25,000 ft. for 7 days (6 hr. per day) in a specially designed chamber. Ethanolic extract of Hypericum perforatum (HPE)(25mg/kg of body weight) was given orally prior to hypoxia exposure and effects were compared to hypoxia and control groups.Results: Animals exposed to hypobaric hypoxia showed sign of cognitive deterioration at day 3 and day 7 in the Elevated Plus Maze and Passive Avoidance Step through behavioral paradigms as compare to normoxic animals. Administration of HPE was able to alleviate the amnesic effect in treatment group, indicated by reduction in transfer latencies at day 3(IR-3 = -0.66±0.07) and day 7 IR-7 = -0.81±0.06) in elevated plus maze task and increased passive avoidance step through latency at day 3, (IR-3 = 3.23±0.67),as compared to ±hypoxic mice. Hypoxia group of animals suffered significant oxidative stress compared to normoxic mice as indicated by up-regulated malondialdehyde and total nitrite levels in hippocampal homogenates. The plasma lactate dehydrogenase activity was also increased following hypoxia indicating tissue damage. Co-treatment with HPE in simulated hypobaric hypoxia insult for seven days resulted in significant reduction in malondialdehyde, total nitrites and plasma LDH levels in animals.Conclusion: Hypericum perforatum extract improves cognitive performance in hypobaric hypoxia exposed mice with a concomitant reduction in oxidative stress burden suggesting its plausible use for preventing high altitude illness.Asian Journal of Medical Sciences Vol.9(2) 2018 1-8


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