Monica L. Andersen

Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats

Since previous data of our group showed increased concentrations in HPA axis hormones in sleep deprived rats, we hypothesized that this augmentation could produce effects in other hormonal systems, particularly in the sexual system. Considering that little is known about how the hormonal system changes during the recovery period after sleep deprivation (SD), our objective was to examine from what point SD alters sexual and stress‐related hormones along with plasma catecholamine concentrations during 4 days. We also sought to verify the time course of their recovery after an equivalent period of recovery sleep. Rats were deprived of sleep by the platform technique for 1–4 days and were allowed to recover for the same period. Plasma catecholamines [dopamine (DA) and noradrenaline (NOR)], testosterone, estrone, progesterone, prolactin, corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured. Comparisons between groups showed that the SD procedure used in the present study produced marked alterations in almost all studied hormones from 24 h of SD, except for estrone and prolactin (which required 96 h of SD to become altered). Testosterone and estrone decreased, whereas progesterone, prolactin, corticosterone, ACTH, DA and NOR increased. During recovery period, progesterone, prolactin and corticosterone concentrations returned to control levels, whereas testosterone, estrone, NOR and DA did not. In addition, after 48 h of recovery ACTH and NOR decreased below control concentrations, remaining low until 96 h of sleep recovery. Thus, SD showed long lasting, differential effects upon these neurochemicals suggesting that each has its own pattern of responses to SD as well as variable periods of recovery.

Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice.

Numerous animal and clinical studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Mice were sleep deprived for 72 h by the multiple platform method-groups of 4-6 animals were placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface. Mice kept in their home cage or placed onto larger platforms were used as control groups. The results showed that hippocampal oxidized/reduced glutathione ratio as well as lipid peroxidation of sleep-deprived mice was significantly increased compared to control groups. The same procedure of sleep deprivation led to a passive avoidance retention deficit. Both passive avoidance retention deficit and increased hippocampal lipid peroxidation were prevented by repeated treatment (15 consecutive days, i.p.) with the antioxidant agents melatonin (5 mg/kg), N-tert-butyl-alpha-phenylnitrone (200 mg/kg) or vitamin E (40 mg/kg). The results indicate an important role of hippocampal oxidative stress in passive avoidance memory deficits induced by sleep deprivation in mice.

Different stress modalities result in distinct steroid hormone responses by male rats

Since both paradoxical sleep deprivation (PSD) and stress alter male reproductive function, the purpose of the present study was to examine the influence of PSD and other stressors (restraint, electrical footshock, cold and forced swimming, N = 10 per group) on steroid hormones in adult Wistar male rats. Rats were submitted to chronic stress for four days. The stressors (footshock, cold and forced swimming) 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 whereas PSD was continuous. Hormone determination was measured by chemiluminescent enzyme immunoassay (testosterone), competitive immunoassay (progesterone) and by radioimmunoassay (corticosterone, estradiol, estrone). The findings indicate that PSD (13.7 ng/dl), footshock (31.7 ng/dl) and cold (35.2 ng/dl) led to lower testosterone levels compared to the swimming (370.4 ng/dl) and control (371.4 ng/dl) groups. However, progesterone levels were elevated in the footshock (4.5 ng/ml) and PSD (5.4 ng/ml) groups compared to control (1.6 ng/ml), swimming (1.1 ng/ml), cold (2.3 ng/ml), and restrained (1.2 ng/ml) animals. Estrone and estradiol levels were reduced in the PSD, footshock and restraint groups compared to the control, swimming and cold groups. A significant increase in corticosterone levels was found only in the PSD (299.8 ng/ml) and footshock (169.6 ng/ml) groups. These changes may be thought to be the full steroidal response to stress of significant intensity. Thus, the data suggest that different stress modalities result in distinct steroid hormone responses, with PSD and footshock being the most similar.

Paradoxical Sleep Deprivation: neurochemical, hormonal and behavioral alterations. Evidence from 30 years of research

Sleep comprises approximately one-third of a persons lifetime, but its impact on health and medical conditions remains partially unrecognized. The prevalence of sleep disorders is increasing in modern societies, with significant repercussions on peoples well-being. This article reviews past and current literature on the paradoxical sleep deprivation method as well as data on its consequences to animals, ranging from behavioral changes to alterations in the gene expression. More specifically, we highlight relevant experimental studies and our groups contribution over the last three decades.

Polysomnographic Study of the Prevalence of Sleep Bruxism in a Population Sample

The goal of the current study was to estimate the prevalence of sleep bruxism (SB) in the general population using a representative sample of 1,042 individuals who answered questionnaires and underwent polysomnography (PSG) examinations. After PSG, the individuals were classified into 3 groups: absence of SB, low-frequency SB, and high-frequency SB. The results indicated that the prevalence of SB, indicated by questionnaires and confirmed by PSG, was 5.5%. With PSG used exclusively as the criterion for diagnosis, the prevalence was 7.4% regardless of SB self-reported complaints. With questionnaires alone, the prevalence was 12.5%. Of the 5.5% (n = 56) with confirmed SB, 26 were classified as low-frequency SB, and 30 as high-frequency. The episodes of SB were more frequent in stage 2 sleep, and the phasic bruxism events were more frequent than tonic or mixed events in all sleep stages in individuals with SB. A positive association was observed between SB and insomnia, higher degree of schooling, and a normal/overweight body mass index (BMI). These findings demonstrate the prevalence of SB in a population sampled by PSG, the gold standard methodology in the investigation of sleep disorders, combined with validated questionnaires (ClinicalTrials.gov, NCT00596713).

Circadian preference in bipolar disorder

PurposeA role for circadian rhythm abnormalities in the pathogenesis of bipolar disorder (BD) has been suggested. The present study assessed circadian preference, a subjective preference for activities in the morning or evening related to chronotype.MethodsThe sample was comprised of 81 outpatients with BD in remission and 79 control subjects. Circadian preference was derived from an interview evaluating biological rhythms and sleep pattern from the Pittsburgh Sleep Quality Index.ResultsPatients were significantly more likely to have an evening preference than control subjects. Circadian preference was also associated with sleep latency.ConclusionsThe association of evening preference and longer sleep latency may be related to the frequent clinical observation of a sleep/wake cycle reversal in bipolar disorder.

Paradoxical sleep deprivation potentiates amphetamine-induced behavioural sensitization by increasing its conditioned component

The effects of paradoxical sleep deprivation (PSD-48 h) on the conditioned and unconditioned components of behavioural sensitization to amphetamine (two injections of 2.0 mg/kg, separated by 7 days) were studied using locomotion frequency of mice observed in an open-field as experimental parameter. Behavioural sensitization only occurred in PS deprived mice that were exposed to the open-field after the first amphetamine injection. The possible involvement of PSD in the development of a Pavlovian association between the stimulant effect of amphetamine and environmental as well as interoceptive drug cues is discussed.

Paradoxical sleep deprivation impairs acquisition, consolidation, and retrieval of a discriminative avoidance task in rats

The aim of the present study was to investigate the effects of paradoxical sleep deprivation (PSD) for 96 h on the learning/memory processes in rats submitted to the plus-maze discriminative avoidance task (PM-DAT), which simultaneously evaluates learning, memory, anxiety and motor function. Four experiments were performed in which rats were submitted to: (1) post-training and pre-test PSD; (2) post-training or pre-test PSD; (3) pre-training PSD or pre-training paradoxical sleep (PS) rebound (24 h) and (4) pre-test PSD rebound. Concerning Experiment I, post-training and pre-test PSD induced memory deficits, an anxiolytic-like behavior and an increase in locomotor activity. In Experiment II, both post-training PS-deprived and pre-test PS-deprived groups showed memory deficits per se. However, only the pre-test PS-deprived animals presented anxiolytic-like behavior and increased locomotor activity. In Experiment III, pre-training PS-deprived rats showed learning and memory deficits, anxiolytic-like behavior and increased locomotor activity. A 24h-sleep recovery period after the PSD abolished the learning and memory deficits but not anxiety and locomotor alterations. Finally, sleep rebound did not modify acquisition (Experiment III) and retrieval (Experiment IV). This study strengthened the critical role of paradoxical sleep (but not sleep rebound) in all the phases of learning and memory formation. In addition, it suggests that PSD effects on acquisition and consolidation do not seem to be related to other behavioral alterations induced by this procedure.

The association of testosterone, sleep, and sexual function in men and women

Testosterone has been the focus of several investigations and review studies in males, but few have addressed its effects on sleep and sexual function, despite evidence of its androgenic effects on circadian activity in both sexes. Studies have been conducted to understand how sleeping increases (and how waking decreases) testosterone levels and how this rhythm can be related to sexual function. This review addresses the inter-relationships among testosterone, sexual function and sleep, including sleep-disordered breathing in both sexes, specifically its effects related to sleep deprivation. In addition, hormonal changes in testosterone that occur in the gonadal and adrenal axis with obstructive sleep apnea and other conditions of chronic sleep deprivation, and which consequently affect sexual life, have also been explored. Nevertheless, hormone-associated sleep disruptions occur across a lifetime, particularly in women. The association between endogenous testosterone and sex, sleep and sleep disturbances is discussed, including the results of clinical trials as well as animal model studies. Evidence of possible pathophysiological mechanisms underlying this relationship is also described. Unraveling the associations of sex steroid hormone concentrations with sleep and sexual function may have clinical implications, as sleep loss reduces testosterone levels in males, and low sex steroid hormone concentrations have been associated with sexual dysfunction.

Pain hypersensitivity induced by paradoxical sleep deprivation is not due to altered binding to brain μ-opioid receptors

Previous studies have established a relationship between sleep disruption and pain, and it has been suggested that hyperalgesia induced by paradoxical sleep deprivation (PSD) could be due to a reduction of opioidergic neurotransmission in the brain. In the present study rats deprived of sleep for 96 h as well as rats allowed to recover for 24h after PSD and normal controls received vehicle or morphine (2.5, 5 and 10 mg/kg, i.p.) and were tested on a hot plate 1h later. Quantitative receptor autoradiography was used to map alterations in binding to brain mu-opioid receptors in separate groups. Results demonstrated that PSD induced a significant reduction in thermal pain threshold, as measured by paw withdrawal latencies. This effect did not return to baseline control values after 24h of sleep recovery. The usual analgesic effect of morphine was observed in the control group but not in PSD or rebound groups except at the highest dose (10 mg/kg). Binding of [3H]DAMGO to mu sites did not differ significantly among the three groups in any of the 33 brain regions examined. These results do not exclude the participation of the opioid system in PSD-induced pain hypersensitivity since sleep-deprived rats were clearly resistant to morphine. However, the fact no changes were seen in [3H]DAMGO binding indicates that mechanisms other than altered mu-opioid binding must be sought to explain the phenomenon.