Tathiana Aparecida Alvarenga

Sleep pattern in rats under different stress modalities.

The present study was designed to evaluate the sleep pattern of rats submitted to chronic stressors (restraint, electrical footshock, swimming and cold) applied to male rats. After 48 h-baseline recording, rats were submitted to 4 days of chronic stress, and electrocorticogram recordings were carried out continuously. The stressors (footshock, swimming and cold) were applied twice a day for periods of 1 h at 9:00 and 16:00 h. Restrained animals were maintained in plastic cylinders for 22 h/day. The findings indicated that sleep efficiency, slow wave sleep (SWS) and paradoxical sleep (PS) were decreased on the third and fourth days of unpredictable shocks compared to baseline while immobilization and swimming presented reduced sleep efficiency in all 4-day recordings. Swimming led to decreased SWS, whereas augmented PS was observed on the first day compared to baseline. Immobilization produced drastic alterations in sleep patterns since it reduced SWS during the 4 days and PS at days 1 to 4 in relation to baseline. Of all stressors, cold was the only one that did not result in any statistical differences in sleep pattern during the light periods. Regarding the effect of stress compared to baseline on the dark recordings, PS was higher during cold stress periods, whereas footshock increased PS on days 2 to 4 and swimming only on day 2. Immobilization decreased PS throughout the 4 days of the stress sessions. Thus, the data suggest that different stress modalities result in distinct sleep responses, with immobilization producing the most dramatic alterations.

Distinct effects of acute and chronic sleep loss on DNA damage in rats

The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.

Effects of sleep loss on sleep architecture in Wistar rats: Gender-specific rebound sleep

This study was designed to examine the influence of gender on sleep rebound architecture after a 4-day paradoxical sleep deprivation period. After a 5-day baseline sleep recording, both male and female rats in different phases of the estrus cycle were submitted to paradoxical sleep deprivation for 96 h. After this period, the sleep rebound recording was evaluated for 5 days (one estrus cycle). The findings revealed that after paradoxical sleep deprivation, sleep efficiency and paradoxical sleep returned to baseline values on the second day of the light period, for all except the proestrus group. During the dark rebound period, only the female groups presented increased sleep efficiency on the first day. Paradoxical sleep returned to baseline values on the third day, except for males and the cycling females submitted to paradoxical sleep deprivation in the diestrus phase, whose baseline values returned to normal on the second day of rebound period. Thus, the females and males displayed distinct patterns as a result of sleep disruption.

Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in intact and ovariectomized rats compared with male rats

The purpose of this study was to investigate the effects of paradoxical sleep deprivation (PSD) on circulating lipoproteins (total cholesterol, HDL, LDL and triglycerides) in males as well as in intact and ovariectomized (OVX) female rats. The intact female rat group was sub-distributed according to the phase of the estrous cycle (proestrus, estrus and diestrus) allowing for comparison of the lipid profile with males and OVX rats. The results indicate that PSD significantly reduced cholesterol in intact females compared to OVX and male rats; it reduced triglycerides in all groups except in diestrus rats and increased HDL levels in male rats compared with the respective controls. PSD also increased LDL levels in male and OVX rats when compared to intact females. Examinations of cholesterol fractions revealed significant increases in HDL in control-OVX animals when compared to the other groups, whereas HDL was significantly increased after PSD in male rats. Such results suggest that the cardiovascular response in intact, OVX females and male rats is differentially regulated especially when such are submitted to PSD. Similarities in blood parameters observed between OVX and male rats are likely due to the suppression of ovarian hormone release after ovariectomy.

Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice

The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

The association between TNF-α and erectile dysfunction complaints.

Inflammatory markers like tumour necrosis factor‐alpha (TNF‐α) have been related to erectile dysfunction (ED) and may interact with other cardiovascular risk factors such as obstructive sleep apnoea syndrome (OSAS). The aim of this study was to examine the inflammatory, metabolic and hormonal profile of men with or without ED complaints and/or OSAS recruited through the Epidemiologic Sleep Study (EPISONO). A sample of 363 men completed sexual questionnaires for ED and had physical and blood examinations. OSAS was evaluated by polysomnography and clinical assessment. The blood samples were used for determination of TNF‐α, interleukin‐6, leptin, cholesterol and fractions, triglycerides, homocysteine, glucose and hormonal levels. After controlling for confounding factors, men with ED complaints presented higher systolic blood pressure and TNF‐α, independent of OSAS. Significant interaction between ED and OSAS was only observed for neck circumference, which was higher in ED men with OSAS than men with OSAS without ED and men with ED without OSAS. Binary logistic regression showed that the predictor factors for ED were age >43 years, myocardial infarction events, TNF‐α and systolic blood pressure. Finally, a receiver‐operating characteristics curve suggested a cut‐off point of 9.95 pg/mL for TNF‐α with sensitivity of 60% and specificity of 59% in men with ED complaints. Furthermore, there was a significant association between high levels of TNF‐α (>9.95 pg/mL) and the presence of ED complaints. The results showed that there was an association between TNF‐α levels and ED complaints in men independent of OSAS.

Sleep Loss Induces Differential Response Related To Genotoxicity in Multiple Organs of Three Different Mice Strains

The purpose of the present study was to determine the genetic damage induced by paradoxical sleep deprivation (PSD) in three different male mice strains in peripheral blood, heart, kidney and liver tissues by the single cell gel (comet) assay. Swiss, C57BL/6j and hairless (HRS/j) mice were submitted to PSD by the multiple platform technique for 72 hr, and DNA damage was evaluated. Statistically significant differences in DNA damage were found in blood cells of the Swiss mice strain when compared to negative controls. By contrast, no statistically significant differences were found in the C57BL/6j or hairless mice strains. With regard to the liver, extensive genotoxic effects were found in the Swiss strain. The hairless and C57BL/6j mice strains did not show any signs of genotoxocity in this organ. The same lack of effect was noted in kidney and heart cells of all strains evaluated. In conclusion, our results reveal that sleep deprivation exerted genetic damage in the form of DNA breakage in blood and liver cells of the Swiss mice strain only. This type of approach should be considered when studying noxious activities on genetic apparatus induced by sleep deprivation in mice since the Swiss strain is more suitable for this purpose.

Anxiety-like effects of meta-chlorophenylpiperazine in paradoxically sleep-deprived mice

Chlorophenylpiperazines (CPP) are psychotropic drugs used in nightclub parties and are frequently used in a state of sleep deprivation, a condition which can potentiate the effects of psychoactive drugs. This study aimed to investigate the effects of sleep deprivation and sleep rebound (RB) on anxiety-like measures in mCPP-treated mice using the open field test. We first optimized our procedure by performing dose-effect curves and examining different pretreatment times in naïve male Swiss mice. Subsequently, a separate cohort of mice underwent paradoxical sleep deprivation (PSD) for 24 or 48h. In the last experiment, immediately after the 24h-PSD period, mice received an injection of saline or mCPP, but their general activity was quantified in the open field only after the RB period (24 or 48h). The dose of 5mgmL(-1) of mCPP was the most effective at decreasing rearing behavior, with peak effects 15min after injection. PSD decreased locomotion and rearing behaviors, thereby inhibiting a further impairment induced by mCPP. Plasma concentrations of mCPP were significantly higher in PSD 48h animals compared to the non-PSD control group. Twenty-four hours of RB combined with mCPP administration produced a slight reduction in locomotion. Our results show that mCPP was able to significantly change the behavior of naïve, PSD, and RB mice. When combined with sleep deprivation, there was a higher availability of drug in plasma levels. Taken together, our results suggest that sleep loss can enhance the behavioral effects of the potent psychoactive drug, mCPP, even after a period of rebound sleep.

Can Ayahuasca and sleep loss change sexual performance in male rats

The ingestion of the beverage Ayahuasca usually occurs in religious ceremonies that are performed during the night leading to sleep deprivation. The purpose of the present study was to characterize the acute effects of Ayahuasca upon the sexual response of sleep deprived male rats. One group of sexually experienced male Wistar rats were submitted to a paradoxical sleep deprivation (PSD) protocol for 96h, while another group spent the same amount of time in the home cage (CTRL). After this period, either saline or Ayahuasca drink (250, 500 and 1000μgmL(-1)) was administered by gavage and sexual behavior and hormonal concentrations were measured. Ayahuasca alone significantly decreased sexual performance at all doses. However, in sleep deprived rats, the lower dose increased sexual performance while the intermediate dose produced a detrimental effect on sexual response compared to the CTRL rats at the same dose. Regarding the hormonal analyses, a lower testosterone concentration was observed in sleep-deprived saline rats in relation to the CTRL group. Progesterone was significantly lower only in PSD rats at the dose 500μgmL(-1) compared with CTRL-500μgmL(-1) group. Corticosterone was unchanged among the groups evaluated. Our results suggest that Ayahuasca intake markedly impaired sexual performance alone, but, when combined with sleep deprivation, had significant, but heterogeneous, effects on male sexual response.

The influence of sleep deprivation on expression of apoptosis regulatory proteins p53, bcl-2 and bax following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

Background: The aim of this study was to evaluate whether paradoxical sleep deprivation could affects the mechanisms and pathways essentials for cancer cells in tongue cancer induced by 4-nitroquinole 1-oxide in Wistar rats. Materials and Methods: For this purpose, the animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 nitroquinoline 1 oxide (4 NQO) solution through their drinking water for 4 and 12 weeks. The animals were submitted to paradoxical sleep deprivation (PSD) for 72 h using the modified multiple platform method, which consisted of placing 5 mice in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. Statistical analysis was performed by Kruskal-Wallis non-parametric test followed by the Dunns test using SPSS software pack (version 1.0). P value < 0.05 was considered for statistic significance. Results: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplasic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53 and for bcl-2 and for all immunomarkers after 12 weeks of 4NQO administration. Conclusion: Our results reveal that sleep deprivation exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.