Effects of sleep deprivation on wound healing.

Sleep deprivation is widely regarded as a stressor and has been shown to have significant effects on host defences. Severely sleep-deprived rats develop lesions on their paws and tails, suggesting possible deficits in the healing process. The purpose of this study was to assess the impact of rapid eye-movement (REM) sleep deprivation (RSD) on wound healing in a rat model. Male dark-hooded Long-Evans rats, 2-4 months old, were subjected to dorsal application of two sterile punch biopsies, each 3.5 mm in size. Biopsies were performed either immediately before or immediately after 5 days of sleep deprivation. Wound healing in REM sleep-deprived animals was compared with home cage control and yoked control animals. RSD did not produce differences in the rate of healing, regardless of the timing of the biopsy punch. RSD does not appear to have significant effects on wound healing and thus appears to act differently from other types of stressors on wound healing.

Fos immunoreactivity in rat subcortical visual shell in response to illuminance changes.

Immediate early gene expression has been used frequently as a marker of activity in the circadian visual system. Recent evidence suggests that the pretectum participates in orchestrating sleep and circadian responses to light. Lesions of the pretectum eliminate dark shift-induced rapid eye movement sleep triggering in albino rats, and compromise circadian phase shifts in hamsters. We hypothesized that regions of the pretectum respond to light with robust and region-specific Fos activation, similar to the suprachiasmatic nucleus and intergeniculate leaflet. We used Fos expression, the protein product of the immediate early gene c-fos, as a functional marker to measure the responses of neurons following acute lighting changes. Rats maintained on a 12:12 light-dark cycle were subjected to a shift from light-to-dark or from dark-to-light at midday (Zeitgeber time 6) or midnight (Zeitgeber time 18). Fos expression was visualized with immunocytochemistry and quantified with an automated scoring system. We found three regions in the pretectum (the olivary pretectal nucleus, posterior limitans, and a region homologous to the hamster commissural pretectal nucleus), and two regions in the lateral geniculate complex (the intergeniculate leaflet and ventral lateral geniculate nucleus) that demonstrated significant Fos activation in response to light. Furthermore, the olivary pretectal nucleus, the posterior limitans, and the ventral lateral geniculate nucleus showed preferential Fos activation after acute light onset rather than following chronic exposure to light at midday, whereas at midnight these nuclei showed Fos activation following both chronic light exposure and acute light onset. Given the extensive anatomical connections between pretectal nuclei and other nuclei in the subcortical visual shell, as well as with centers for sleep and arousal, it is highly plausible that these pretectal nuclei integrate information about changes in illuminance, and aid in the coordination of acute behavioral responses to light.

Sleep and behavior problems in school-aged children.

OBJECTIVES: The primary purposes of the present study were to survey the prevalence of sleep problems in school-aged children and to examine these associations with parental perception of sleep problems, medical history, and childhood psychopathology. METHODS: Sleep and medical history questionnaires and the Child Behavior Checklist were administered to the parents of 472 children between ages 4 and 12 years receiving routine pediatric care from urban, rural, and suburban pediatric practices. RESULTS: Although sleep problems were reported for 10.8% of the sample during the past 6 months, less than one half of the parents who identified sleep problems reported that they had discussed sleep with their child's pediatrician. The best predictor of current sleep problems was a history of sleep problems before age 2 years. Sleep problems such as snoring, tiredness during the day, and taking excessive time to fall asleep were very common, occurring at least 1 night per week in over 20% of the total sample. Factor analysis of the sleep problems questionnaire resulted in 5 sleep problem factors that accounted for 58.7% of the variance. Specific sleep problem factors include: parasomnias, enuresis/gags, tiredness, noisy sleep, and insomnia. Sleep problem factor scores were differentially associated with medical history variables and measures of childhood psychopathology. Children rated highly on parasomnias were more likely to have frequent falls and to display pica. Parasomnias and noisy sleep were inversely associated with socioeconomic status (SES). Children from lower SES families were rated higher on these factors than children from higher SES families. Enuresis/gags was the only sleep problem factor associated with age. Younger children scored higher on this factor. Duration of naps was highly correlated with age and with bed times during the week and weekends. As expected, younger children were more likely to nap for longer periods and to have earlier bed times. In addition, higher tiredness factor scores were associated with napping and with later bed times during the week and weekend. Boys were much more likely than were girls to have higher scores on enuresis/gags, and higher enuresis/gags scores were associated with an increased prevalence of trauma and falls. Bed times were not associated with any other sleep problem factor score. Children rated highly on tiredness were more likely to have a history of hospitalizations. Tiredness factor scores were strongly associated with the sleep practice of sharing a bed but not with sharing a room. Sharing a room was not associated with any sleep problem factor score. High scores on noisy sleep were associated with allergies, falls frequently, and with sharing a bed. Children with high scores on the insomnias were also more likely to display an increased prevalence of allergies. CONCLUSIONS: Parental perception of global sleep problems was surprisingly common in school-aged children receiving routine pediatric care. Parental reports of their children's sleep problems may be a red flag for specific sleep problems and psychiatric, social, or medical problems. Sleep problems should be queried about during pediatric visits for school-aged children.

Effects of amygdala lesions on sleep in rhesus monkeys.

The amygdala is important in processing emotion and in the acquisition and expression of fear and anxiety. It also appears to be involved in the regulation of sleep and wakefulness. The purpose of this study was to assess the effects of, fiber-sparing lesions of the amygdala on sleep in rhesus monkeys (Macaca mulatta). We recorded sleep from 18 age-matched male rhesus monkeys, 11 of which had previously received ibotenic acid lesions of the amygdala and seven of which were normal controls. Surface electrodes for sleep recording were attached and the subjects were seated in a restraint chair (to which they had been adapted) for the nocturnal sleep period. Despite adaptation, control animals had sleep patterns characterized by frequent arousals. Sleep was least disrupted in animals with large bilateral lesions of the amygdala. They had more sleep and a higher proportion of rapid-eye-movement (REM) sleep than did either animals with smaller lesions or control animals. Based on these results, it seems likely that, in the primate, the amygdala plays a role in sleep regulation and may be important in mediating the effects of emotions/stress on sleep. These findings may also be relevant to understanding sleep disturbances associated with psychopathology.

The pretectum mediates rapid eye movement sleep regulation by light.

A variety of sensory stimuli (e.g., visual, auditory, and thermal) are known to induce rapid eye movement (REM) sleep in mammals. Studies have examined the induction of REM sleep in albino rats by light-to-dark transitions, a phenomenon referred to as REM sleep triggering. Recent research has demonstrated that aspiration lesions of the superior colliculus (SC) and pretectal area attenuated REM sleep triggering. To define more specifically the area or areas involved in mediating REM sleep responses to changes in illumination, fiber-sparing neurotoxic lesions were made to the pretectum (PT) or the SC. Lesions of the PT attenuated REM sleep triggering, whereas lesions of the SC did not. Thus, the role of the PT may be expanded to include the regulation of REM sleep in response to photic stimulation in albino rats. These findings provide a paradigm in which to study mechanisms of REM sleep generation and the effects of light on behavioral state.

EEG alpha power and alpha power asymmetry in sleep and wakefulness.

Asymmetry of waking electroencephalography (EEG) alpha power in frontal regions has been correlated with waking emotional reactivity and the emotional content of dream reports. Little is known regarding alpha asymmetry during sleep. The present study was performed to compare alpha power and alpha power asymmetry in various brain regions across states of sleep and wakefulness. Waking and sleep EEG were recorded in a group of patients undergoing polysomnographic evaluation for possible sleep disorders. Alpha EEG asymmetry in frontal and temporal regions was significantly correlated in waking versus sleep, particularly during rapid eye movement (REM) sleep. These results suggest that patterns of frontal alpha asymmetry are stable across sleep and waking and may be related to emotional reactivity during dreaming. During sleep, alpha power was highest during slow-wave sleep and lowest during REM sleep. Implications of these data for understanding the functional significance of alpha power during waking and sleeping are considered.

REM sleep in response to light and dark in congenic albino and pigmented F344 rats.

Sleep was recorded in congenic F344 albino (c/c) and pigmented (c/+) rats while they were exposed to various light-dark schedules at 10, 50 and 100 lux. In short LD schedules (1:1 and 3:3), both c/c and c/+ rats had similar patterns of NREM and waking in the light and dark. NREM was higher in the light and there was more wakefulness in the dark. These differences were accentuated with increased light intensity. In contrast, substantial effects on REM sleep were seen only in the c/c rats and increased light levels also enhanced these effects. REM sleep in pigmented c/+ rats was virtually unaffected by lighting changes. These results indicate that different systems are involved in regulating sleep-waking and REM sleep responses to light and further that these systems are differentially affected by alleles at (or near) the c locus and/or albinism.

Effects of lighting conditions on sleep and wakefulness in albino Lewis and pigmented Brown Norway rats.

STUDY OBJECTIVES: Previous studies have demonstrated that albino but not pigmented rats show acute increases in REM sleep following light-to-dark transitions. Light and dark have also been shown to have direct effects on NREM sleep and wakefulness in albino rats. Little is known, however, about the direct light-dark effects on sleep patterns in pigmented animals. The purpose of the present study was to compare the direct effects of light and dark on REM sleep, NREM sleep, and waking in albino Lewis and pigmented Brown Norway (BN) rats. DESIGN: Groups of albino Lewis and pigmented Brown Norway (BN) rats were exposed to various light-dark (LD) schedules. In the first experiment, the lighting schedules were LD 12:12 and LD 3:3. The second experiment compared LD 12:12 with an irregular schedule consisting of short light and dark periods of unequal length. MEASUREMENTS AND RESULTS: Both Lewis and BN rats slept more during the light and were awake more during the dark on all schedules. REM sleep patterns in light and dark periods were opposite, however. Lewis rats spent more of their sleep in REM sleep during dark than the light, whereas BN rats had a higher proportion of REM sleep in the light. CONCLUSIONS: The results suggest that there are substantial direct effects of light and dark on sleep in pigmented as well as in albino rats, although these effects are not always the same in magnitude or even in direction.

The superior colliculus-pretectum mediates the direct effects of light on sleep.

Light and dark have immediate effects on sleep and wakefulness in mammals, but the neural mechanisms underlying these effects are poorly understood. Lesions of the visual cortex or the superior colliculus-pretectal area were performed in albino rats to determine retinorecipient areas that mediate the effects of light on behavior, including rapid eye movement sleep triggering by lights-off and redistribution of non-rapid eye movement sleep in short light-dark cycles. Acute responses to changes in light conditions were virtually eliminated by superior colliculus-pretectal area lesions but not by visual cortex lesions. Circadian entrainment was evident in both groups with lesions and in normal controls. Thus, acute light-dark effects on sleep and wakefulness appear to be mediated independently from cortical vision or circadian rhythms.

Sleep and mood disorders.

Mood disorders are found in one-third to one-half of patients with chronic sleep problems. Likewise, most patients with mood disorders experience insomnia, but a minority obtain significantly increased amounts of sleep. Although mood disorders cause significant morbidity and mortality, they often go undiagnosed. Attention to sleep complaints could lead to better identification of mood disorders. Management of sleep problems in patients with mood disorders should focus on treating underlying mood disorders with attention to the nature of the sleep complaint. Patients with depression show characteristic abnormalities in sleep continuity, slow-wave sleep and REM sleep patterns. Differences in sleep patterns cannot reliably distinguish patients with depression from those with other psychiatric disorders, but sleep changes may provide a window on neurobiologieal abnormalities in depression.

Analysis of the retinohypothalamic tract in congenic albino and pigmented rats.

To determine whether differences in the retinohypothalamic tract (RHT) were related specifically to albinism, we analyzed the distribution and trajectory of this pathway in congenic F344-c/+ albino and pigmented rats using the inactive subunit of cholera toxin conjugated to horseradish peroxidase as an anterograde tracer. We found that the overall volume of the tract in the albino rats was greater than in the pigmented rats (P < 0.05). We also noted shape differences.

Effects of drugs on sleep.

Many commonly prescribed medications and substances of abuse can have significant effects on sleep and wakefulness. Chronic use or abuse of certain drugs may lead to the development of substance-related sleep disorders. Primary sleep disorders, such as apnea, periodic movement disorders, and parasomnias, may be exacerbated by various drugs. This article summarizes the effects of widely used medications and recreational drugs on sleep.

Increased basal REM sleep but no difference in dark induction or light suppression of REM sleep in flinders rats with cholinergic supersensitivity.

Increased cholinergic sensitivity in the central nervous system has been postulated to account for some of the neuroendocrine abnormalities and sleep disturbances seen in human depressives. The Flinders Sensitive Line (FSL) rats, which exhibit increased sensitivity to cholinergic agents, have been shown to have REM sleep patterns similar to those seen in depressives, including shorter REM sleep latency and increased daily percentage of REM sleep. We studied the response of FSL and control rats to brief dark pulses administered during the normal light period (which are known to stimulate REM sleep in albino rats) and to brief light pulses during the normal dark period (which suppress REM sleep in albino rats) to determine whether these responses are affected by central cholinergic hypersensitivity. FSL rats showed REM sleep patterns indistinguishable from controls during light or dark pulses, which does not support the primary involvement of cholinergic systems in this mechanism of REM sleep regulation. We also examined REM and non-REM (NREM) sleep patterns in FSL rats and their controls to determine whether they show sleep continuity disturbances or decreased sleep intensity as seen in depression. In agreement with an earlier study, we found that FSL rats had more daily REM sleep and accumulated less NREM sleep between REM bouts than controls. Duration of NREM sleep bouts, total daily NREM sleep time, and EEG amplitude of NREM sleep did not differ between FSL and control rats, suggesting that the cholinergic abnormalities in FSL rats do not produce substantial NREM sleep changes.

Failure to induce rapid eye movement sleep by dark pulses in pigmented inbred rat strains.

Studies of albino Lewis rats, pigmented Brown Norway rats, and their F2 backcross progeny have demonstrated that the ability to trigger rapid eye movement (REM) sleep by turning off cage lights (dark pulses) is associated with albinism in these rat strains. Other studies have shown that pigmented inbred rats show REM sleep induction in the dark portion of short light:dark cycles or skin temperature changes. In the present study, these same pigmented breeds, Dark Agouti and hooded Long-Evans rats, were subjected to 5-min dark pulses and failed to show any evidence of REM sleep triggering. In fact, they showed trends towards REM sleep suppression during dark pulses. These results extend the finding that dark pulse triggering of REM sleep, readily evoked in albino rats, does not appear in pigmented rat strains.

Sleep and psychiatric disorders. A meta-analysis.

We reviewed the literature on sleep in psychiatric disorders and evaluated the data by meta-analysis, a statistical method designed to combine data from different studies. A total of 177 studies with data from 7151 patients and controls were reviewed. Most psychiatric groups showed significantly reduced sleep efficiency and total sleep time, accounted for by decrements in non-rapid eye movement sleep. Rapid eye movement sleep time was relatively preserved in all groups, and percentage of rapid eye movement sleep was increased in affective disorders. Reduction in rapid eye movement sleep latency was seen in affective disorders but occurred in other categories as well. Although no single sleep variable appeared to have absolute specificity for any particular psychiatric disorder, patterns of sleep disturbances associated with categories of psychiatric illnesses were observed. Overall, findings for patients with affective disorders differed most frequently and significantly from those for normal controls.