Paula Araujo

Single exposure to cocaine or ecstasy induces DNA damage in brain and other organs of mice

We evaluated the overall genetic damage induced by different doses of cocaine and MDMA (3,4‐Methylenedioxymethamphetamine) in several organs. One hour after intraperitoneal drug administration, mice were euthanized; peripheral blood, liver and brain were collected, and the cellular suspensions were used for the single cell gel (comet) assay. We determined that all doses of cocaine and MDMA tested were able to induce DNA damage in blood cells. Extensive genotoxic damage was induced by cocaine or MDMA at the highest doses used in liver cells. Brain cells were affected by all doses administrated. These findings demonstrate that cocaine and MDMA are potent genotoxins.

Neonatal exposure to constant light prevents anhedonia-like behavior induced by constant light exposure in adulthood

Depressive episodes are associated with disturbances in circadian rhythms, and constant illumination has been reported to induce depressive-like behavior in rodents. Rats kept in constant darkness express the endogenous circadian rhythm, and most animals under constant light conditions lose circadian locomotor rhythmicity. Exposure to constant light in rats during lactation was reported to prevent this loss of circadian rhythm in adulthood. Thus, the aim of the present study was to verify whether exposure to constant light during lactation prevents anhedonia-like behavior induced by constant light in adult rats. In experiment 1, we replicated the anhedonia-like effects of constant light in adult male rats. We showed that this effect is reversed by imipramine treatment in the drinking water. In experiment 2, we subjected rats to constant darkness (neonatal-DD), constant light (neonatal-LL) or to normal light/dark cycle (neonatal-LD) during the neonatal phase and evaluated them after constant light exposure in adulthood. The group exposed to constant light during the neonatal phase did not reduce their sucrose preference and exhibited greater locomotor activity than the other groups. The neonatal-DD group exhibited decreased sucrose preference earlier than controls and had higher serum corticosterone concentrations. Prevention of arrhythymicity might protect neonatal-LL rats from anhedonia-like behavior induced by constant light, whereas constant darkness during the neonatal phase rendered the neonatal-DD group more susceptible to depressive-like behavior. These results corroborate with the literature data indicating that circadian disruption may contribute in mood disorders and that early life stress can influence stress responsivity in adulthood.

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.

Sleep pattern in an experimental model of chronic kidney disease

The prevalence of sleep disorders is significantly elevated in chronic kidney disease (CKD) patients. Numerous factors likely contribute to the high prevalence of sleep problems in uremic patients. The objective of this study was to evaluate the long-term sleep pattern changes in uremic rats during disease progression. Sleep recordings of the rats were monitored during light and dark periods that lasted 12 h each. These recordings were performed on days 7, 30, 60, and 90 after CKD induction. Cardiovascular, hormonal, and biochemical changes were evaluated at these same time points in control and uremic rats. CKD progression was reflected by the presence of hypertension and progressive increases in urea, creatinine, and cholesterol levels. We also observed hormonal fluctuations of corticosterone and ACTH, which indicated a potential alteration in the hypothalamic-pituitary-adrenal axis in diseased rats. In addition, rats with CKD demonstrated fragmented sleep with a greater number of arousals and decreased sleep efficiency in the light period during disease progression. In the dark period, there was an initial increase in sleep efficiency in CKD rats, but after 90 days of CKD, these animals slept less compared with the control group. Collectively, these metabolic and cardiovascular changes were associated with the persistent alterations in sleep architecture observed in CKD rats.

Impact of sex on hyperalgesia induced by sleep loss

This study evaluated the impact of sex on the short term consequences of different periods of sleep deprivation and the effect of the respective sleep recovery periods on nociceptive responses. Male and female C57BL/6J mice were assigned to the following groups: paradoxical sleep deprived (PSD) for 72 h, sleep restricted (SR) for 15 days, exposed to respective recovery periods for 24 h, or untreated home-cage controls (CTRL). Mice were submitted to a noxious thermal stimulus to evaluate their nociceptive response after PSD, SR, or recovery periods. Blood was collected for hormonal analysis. The nociceptive response was significantly lower in PSD and SR mice compared to CTRL animals, regardless of the sex. However, SR females had a lower paw withdrawal threshold than males. Sleep recovery was able to restore normal nociceptive sensitivity after PSD in both sexes. The hyperalgesia induced by SR was not reversed by sleep rebound. In females, low concentrations of estradiol were found after SR, and these concentrations continued to decrease after 24 hours of sleep recovery. The PSD male mice exhibited higher concentrations of corticosterone than the CTRL and SR male mice. Corticosterone levels were not affected by SR. Our study revealed that PSD and SR induce hyperalgesia in mice. The SR groups showed marked changes in the nociceptive response, and the females were more sensitive to these alterations. This finding indicates that, although different periods of sleep deprivation change the nociceptive sensitivity in male and female mice, sex could influence hyperalgesia induced by chronic sleep loss.

Sex differences in sleep pattern of rats in an experimental model of osteoarthritis

Background: Osteoarthritis (OA) is a major healthcare burden with increasing incidence, and is characterised by the degeneration of articular cartilage. OA is associated with chronic pain and sleep disturbance.

Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones.

Sleep pattern in women with menstrual pain

BACKGROUND Menstrual pain is a common problem in women of reproductive age and often interferes with the ability to work and with general well-being. Because painful conditions frequently affect sleep, we investigated the impact of this menstrual disorder on sleep patterns in adult women. Additionally, we examined whether medications used to alleviate menstrual pain promoted changes in sleep. METHODS According to their hormone profiles and menstrual histories, a total sample of 24 women (25-48 years old) who were experiencing their menstrual periods on the day of the polysomnogram (PSG) were included in the study. All of the participants answered questions regarding the presence of menstrual pain and use of medication. RESULTS Menstrual pain was reported by 66.6% of the women on the night of the PSG. No marked effects were observed on the sleep pattern of these subjects compared with women without menstrual pain. The use of medication did not promote significant changes in the sleep pattern. None of the women were taking oral contraceptives. CONCLUSIONS The presence of menstrual pain or the use of medication to alleviate pain did not significantly alter sleep patterns. Thus, the results suggest that the presence of self-described menstrual pain does not affect sleep patterns in adult women.

Association of methamidophos and sleep loss on reproductive toxicity of male mice

This study investigated the effects of organophosphate exposure on the male reproductive system of mice submitted to chronic sleep loss condition. Adult Swiss mice were distributed into 4 groups: control; methamidophos (MTP); sleep restriction (SR); and MTP+SR. The dose of methamidophos was 0.002 mgkg(-1)day(-1) (half of the Acceptable Daily Intake). Sleep restriction condition was 21 h day(-1) during 15 days. In relation to control group, MTP treatment induced a significant reduction of 12% on morphologically normal spermatozoa in both MTP and MTP+SR groups. In addition, the absolute and relative weights of the seminal vesicles were decreased (MTP, -34%; MTP+SR, -45%). Epididymal fat was reduced in SR groups (SR, -64%; MTP+SR, -58%). Plasma testosterone levels were significantly decreased in MTP and SR groups, and progesterone levels were increased 8 times in MTP+SR in comparison with the control group. The corticosterone levels were unaffected by MTP or SR conditions. Thus, low dose MTP exposure resulted in deleterious effects on the male reproductive system. Sleep loss associated with MTP potentiated the effect on steroidogenesis, mainly in terms of progesterone levels.

Fibromyalgia and sleep in animal models: a current overview and future directions.

Sleep disorders are highly prevalent in patients with fibromyalgia (FM). Many of the daytime symptoms, such as chronic pain and fatigue, may be related to the non-restorative sleep patterns associated with the disease. Pain influences the sleep process and sleep disturbances decrease the pain threshold in a reciprocal framework. Thus, understanding the link between sleep and FM has become an important research topic in basic science. Therefore, in the current review we connect these topics and provide some insights into the cyclic relationship between sleep and pain, which has been addressed mainly in animal models. Additionally, we highlight the urgent need for sleep studies in FM animal models, which might improve the knowledge base and accelerate advances in this field.