Global slowing of network oscillations in mouse neocortex by diazepam

SCHEFFZUK, C. , KUKUSHKA, V. , VYSSOTSKI, A. L. , DRAGUHN, A. , TORT, A. B. L. , BRANKACK, J. . Global slowing of network oscillations in mouse neocortex by diazepam. Neuropharmacology , v. 65, p. 123-133, 2013.

Investigação do papel modulador do Haloperidol sobre os níveis de proteínas relacionadas à plasticidade e preferência por objetos novos em camudongos

Dopamine (DA) is known to regulate both sleep and memory formations, while sleep plays a critical role in the consolidation of different types of memories. We believe that pharmacological manipulation of dopaminergic pathways might disrupt the sleep-wake cycle, leading to mnemonic deficits, which can be observed in both behavioral and molecular levels. Therefore, here we investigated how systemic injections of haloperidol (0.3 mg/kg), immediately after training in dark and light periods, affects learning assessed in the novel object preference test (NOPT) in mice. We also investigated the hippocampal levels of the plasticity-related proteins Zif-268, brain-derived neurotrophic factor (BDNF) and phosphorylated Ca2+/calmodulin-dependent protein kinases II (CaMKII-P) in non-exposed (naïve), vehicle-injected controls and haloperidol-treated mice at 3, 6 and 12 hours after training in the light period. Haloperidol administration during the light period led to a subsequent impairment in the NOPT. In contrast, preference was not observed during the dark period neither in mice injected with haloperidol, nor in vehicle-injected animals. A partial increase of CaMKII-P in the hippocampal field CA3 of vehicle-injected mice was detected at 3h. Haloperidol-treated mice showed a significant decrease in the dentate gyrus of CaMKII-P levels at 3, 6 and 12h; of Zif-268 levels at 6h, and of BDNF levels at 12h after training. Since the mnemonic effects of haloperidol were only observed in the light period when animals tend to sleep, we suggest that these effects are related to REM sleep disruption after haloperidol injection

Dinâmica da Plasticidade Sináptica em neurônios do hipocampo durante ciclos de sono: um estudo computacional

Several research lines show that sleep favors memory consolidation and learning. It has been proposed that the cognitive role of sleep is derived from a global scaling of synaptic weights, able to homeostatically restore the ability to learn new things, erasing memories overnight. This phenomenon is typical of slow-wave sleep (SWS) and characterized by non-Hebbian mechanisms, i.e., mechanisms independent of synchronous neuronal activity. Another view holds that sleep also triggers the specific enhancement of synaptic connections, carrying out the embossing of certain mnemonic traces within a lattice of synaptic weights rescaled each night. Such an embossing is understood as the combination of Hebbian and non-Hebbian mechanisms, capable of increasing and decreasing respectively the synaptic weights in complementary circuits, leading to selective memory improvement and a restructuring of synaptic configuration (SC) that can be crucial for the generation of new behaviors ( insights ). The empirical findings indicate that initiation of Hebbian plasticity during sleep occurs in the transition of the SWS to the stage of rapid eye movement (REM), possibly due to the significant differences between the firing rates regimes of the stages and the up-regulation of factors involved in longterm synaptic plasticity. In this study the theories of homeostasis and embossing were compared using an artificial neural network (ANN) fed with action potentials recorded in the hippocampus of rats during the sleep-wake cycle. In the simulation in which the ANN did not apply the long-term plasticity mechanisms during sleep (SWS-transition REM), the synaptic weights distribution was re-scaled inexorably, for its mean value proportional to the input firing rate, erasing the synaptic weights pattern that had been established initially. In contrast, when the long-term plasticity is modeled during the transition SWSREM, an increase of synaptic weights were observed in the range of initial/low values, redistributing effectively the weights in a way to reinforce a subset of synapses over time. The results suggest that a positive regulation coming from the long-term plasticity can completely change the role of sleep: its absence leads to forgetting; its presence leads to a positive mnemonic change

Funcionalidade em pacientes após acidente vascular encefálico: relação com o sono e ritmo de atividade-repouso

It is known that sleep plays an important role in the process of motor learning. Recent studies have shown that the presence of sleep between training a motor task and retention test promotes a learning task so than the presence of only awake between training and testing. These findings also have been reported in stroke patients, however, there are few studies that investigate the results of this relationship on the functionality itself in this population. The objective of this study was to evaluate the relationship between functionality and sleep in patients in the chronic stage of stroke. A cross-sectional observational study was conducted. The sample was composed of 30 stroke individuals in chronic phase, between 6 and 60 months after injury and aged between 55 and 75 years. The volunteers were initially evaluated for clinical data of disease and personal history, severity of stroke, through the National Institute of Health Stroke Scale, and mental status, the Mini-Mental State Examination. Sleep assessment tools were Pittsburgh Sleep Quality Index, the Questionnaire of Horne and Ostberg, Epworth Sleepiness Scale, the Berlin questionnaire and actigraphy, which measures were: real time of sleep, waking after sleep onset, percentage of waking after sleep onset, sleep efficiency, sleep latency, sleep fragmentation index, mean activity score. Other actigraphy measures were intraday variability, stability interdiária, a 5-hour period with minimum level of activity (L5) and 10-hour period with maximum activity (M10), obtained to evaluate the activity-rest rhythm. The Functional Independence Measure (FIM) and the Berg Balance Scale (BBS) were the instruments used to evaluate the functional status of participants. The Spearman correlation coefficient and comparison tests (Student's t and Mann-Whitney) were used to analyze the relationship of sleep assessment tools and rest-activity rhythm to measures of functional assessment. The SPSS 16.0 was used for analysis, adopting a significance level of 5%. The main results observed were a negative correlation between sleepiness and balance and a negative correlation between the level of activity (M10) and sleep fragmentation. No measurement of sleep or rhythm was associated with functional independence measure. These findings suggest that there may be an association between sleepiness and xii balance in patients in the chronic stage of stroke, and that obtaining a higher level of activity may be associated with a better sleep pattern and rhythm more stable and less fragmented. Future studies should evaluate the cause-effect relationship between these parameters

Qualidade de sono e qualidade de vida em trabalhadores submetidos a diferentes esquemas de trabalho de uma empresa petroquímica

One of the largest problems of the present time resulting from the economic globalization and the modern technology, of the point of view of the biological rhytms of our organism, it is offering services and production of goods available in 24 o'clock, that it demands organized workers in several work schedules besides the hours of the day. Those schedules cause a series of biopsychosocial consequences in the worker's health, in function of circadian, homeostatic and psychosocial alterations. Accordingly, the aim of this study was to accomplish an evaluation of the effects of several works schedules in the pattern of the sleep wake cycle, anxiety, stress and in the health. We counted with a sample of 274 workers subdivided in 49 daytime worker groups and 225 workers in different shift work schedules with different speeds (rotating shift group, slower day shift group, faster day shift group). From the results analysis it is verified irregularities of the daily activities, stress and alterations in the workers' health in all schedules. It was also verified thata the workers thata presented irregularities in the daily activities were the mroe stressed. On the other hand, the shift works were considered more ansious and associated with bad sleep quality. It was verified that the workers with bad sleep quality were those presented larger levels of dispocional anxiety. There was no statistically significant correlation between bad sleep quality and irregular daily lifestyle. However, it can be affirmed thata shift work schendules doesn't are the main determinant for the circadian alterations, but the answers of the individuals to the shifts work; and that the inadequate behavioural strategies to work with the effects of the shift schedules. In conclusion, individual strategies related to the coping of the work in shift (adaptation and tolerance) should be extolled as indispensable tool in the ergonomic evaluation of the work

Estratégias para ajuste do ciclo vigília-sono de adolescentes aos horários escolares matutinos: a educação sobre o sono e a exposição a luz solar

In adolescents, who tend to sleep and wake-up later, the school schedule in the morning is associated with sleep advancement and shortening besides bedtime and wake-up time irregularity between week and weekend days. As a result, there is an increase in daytime sleepiness and a drop in cognitive performance that interfer in students performance in classroom. These consequences reinforce the need to evaluate alternatives that help the adolescent to adapt their sleep needs to the time of start of classes in the morning. Accordingly, the general aim of this study was to evaluate the effects of a sleep program education and sunlight exposure in early morning on sleep-wake cycle (SWC) and daytime sleepiness of adolescents. The students chronotype were evaluated by the Horne-Ostberg questionnaire and the health and usual sleep habits by "the health and the sleep questionnaire. The SWC patterns were assessed by sleep log, the daytime sleepiness by Karolinska Sleepiness Scale (KSS) and the alertness by the Psychomotor Vigilance Test (PVT). These parameters were compared before and after a sleep education program and before and during the sunlight exposure. The sleep program was effective in increasing sleep knowledge of adolescents, in promoting a reduction of bedtime and wake-up time irregularity and increasing the sleep duration in school days. The sunlight exposure effect was evaluated in the return to classes after vacation due to the difference in sleep patterns between school and vacation days. During the intervention week it was observed an advance of sleep schedules, an increase on sleep duration and alertness at the end of the morning. Assessed separately, sleep education and sunlight exposure should contribute to minimize adolescents partial sleep deprivation, but daytime sleepiness effect must be better investigated. These strategies should be used jointly by school members to improve health and performance of their students

Caracterização do ritmo de atividade motora durante a puberdade em sagüis (Callithrix jacchus) sob condições semi-naturais

Most of ontogenetic studies on circadian timing system have been developed on infants, adults and elderly. The puberty has not been a stage of life few studied, except for researches in human adolescents, that presents phase delay in sleep-wake cycle. However, few studies have focused on the basis of this circadian change due to methodological difficulties. Thus, an animal model to study the sleep-wake cycle at puberty is essential. In the common marmoset, a social primate, the circadian activity periodicity stabilizes around 4 months (juvenile stage) and the 8h period component has a seasonal variation. Puberty stage of this species begins near the 8th month of age in males and near the 7th month in females with 7 months of duration. With the aim to characterize the circadian motor activity rhythm during puberty in marmosets (Callithrix jacchus) the motor activity was continuous registered by actiwatches in 6 animals between 5-12 months. Since the social factor influence the behavior of this specie, behavioral observations were realized in 30 minutes windows twice/week to a general evaluation of the influence social interactions dynamic across experiment. Determination of puberty onset was done by fecal progesterone and estrogens in females, and androgens in males. From the analysis of the multiple regression test was selected a model that evaluate age and seasonal variables effect on the activity rhythm according to the higher explanation coefficient. The total activity was the only parameter influenced by age. Moreover, the activity onset was the parameter more explained by the model, and the sunrise was the factor that most influenced it. After the puberty onset, 2 dyads advanced the activity onset. The activity total decreased in 1 dyad and increased in 2 dyads. This increase may be related to the birth of infants in these families. The motor activity circadian component stabilized later in 1 dyad, coinciding with the puberty onset of these animals, while bimodality, caused by the 8 h component, was modulated by seasonality. The agonistic behavior was not evaluated due to reduced number of events. There were changes across ages in affiliative behavior of contact in 1 dyad, grooming done in 1 animal and grooming received in 2 animals. Although there is evidence of puberty effect on the activity motor rhythm, the photoperiodic fluctuations influenced the rhythm. Therefore is not possible to affirm if the puberty modulate the activity rhythm in marmosets

Efeito do exercício físico matinal realizado sob luz solar no ciclo vigília-sono de adolescentes

The sleep onset and offset delay at adolescence in relation to childhood. Besides biological causes, some external factors as academic obligations and socialization contributes, increasing the burden of school and socialization. However, morning school schedules reduce sleep duration. Besides light strong effect, studies in humans have indicated that exercise influence circadian synchronization. To evaluate the effect of the morning exercise under sunlight on sleep-wake cycle (SWC) of adolescents, 160 high school students (11th year) were exposed to the following conditions: lesson in usual classroom (Group C), lesson in swimming pool exposed to sunlight (Group E), half of them carrying through physical activity (EE) and the other resting (EL). Each experimental group met two stages: assessment of SWC 1 week before and 1 week during the intervention, which was held in Monday and Wednesday between 7:45 and 8:30 am. In the baseline, there were applied the questionnaires "Health and Sleep" and cronotype evaluation (H & O). In addition, students were evaluated before and during the intervention by "Sleep Diary", "Karolinska Sleepiness Scale" (KSS), Psychomotor Vigilance Test (PVT) and actimetry. During the intervention, there was a delay in wake-up time on the weekend and a trend to greater sleep duration on week for the three groups. At the weekend, only the groups EE and EL increased sleep duration. There was no difference in bedtime, irregularity of sleep schedules and nap variables. The sleepiness showed a circadian pattern characterized by higher alertness levels at 11:30 am and sleepiness levels at bedtime and wake-up time on week. On weekends there were higher levels of alertness in these times. In the days of intervention, there was an increase of sleepiness at 11:30 am for groups EL and EE, which may have been caused by a relaxing effect of contact with the water of the pool. In addition, the group EE showed higher alert levels at 14:30 pm on Monday and at 8:30 am in the Wednesday, possibly caused by exercise arousal effect. The reaction time assessed through the TPV did not vary between the stages. The sleep quality improved in the three groups in the second stage, making impossible the evaluation of intervention effect. However, the sleep quality increased on Monday and Tuesday only on the group EE. From the results, it is suggested that the intervention promoted effects on the sleepiness at some day hours. In other SWC variables there were no effects, possibly due to a large SWC irregularity on weekends. Thus, the evaluation of higher weekly frequency EF is necessary, since only two days were insufficient to promote greater effect on adolescents SWC

Qualidade subjetiva do sono e queixa de insônia em pacientes com Acidente Vascular Cerebral

Brain injury can be associated with changes in the sleep-wake cycle. However, studies about sleep disturbances and their relationship with quality of sleep are scarce. Besides, it remains to be known how stroke affects the mechanisms of sleep. The aim of this study was to investigate quality of sleep, complaints of sleep disturbances and associated factors in stroke patients from the Physical Therapy services in Natal -RN. This was a cross-sectional descriptive study involving 70 individuals (aged 45-65 years), 40 patients (57 ± 7 years), 11 ± 9 months after injury, and 30 healthy individua ls (52 ± 6 years), evaluated with the Pittsburgh Sleep Quality Index (PSQI) and Sleep Habits Questionnaire. The data were analyzed by Chi-square test, t Student test and logistic regression. Poor quality sleep was found in 57,5% of the patients (6,3 ± 3,5) and was significantly higher than in the control population (3,9 ± 2,2) (t Student test, p=0,002). The patients showed significantly higher value of PSQI than controls: sleep latency (p=0,019), length of sleep (p=0,039) and dysfunction during the day (p=0,001). Regarding complaints of sleep disturbances (dyssomnias and parasomnias) analyzed by Chi-square test, the complaint of insomnia was the most prevalent (patients: 37,5%; healthy subjects: 6,7%; p=0,007). Regression analysis showed that sl eep latency (p=0,036) and complaint of insomnia (p=0,036) were associated with quality sleep. In addition, female gender (p=0,036) and complaint of broken sleep (p=0,003) were considered risk factors for the presence of insomnia. Our results show that stroke affects the homeostatic process of sleep. Shorter sleep latency and the absence of insomnia are considered protective factors for good sleep quality and this should be taken into consideration in the diagnostic and therapeutic strategies

Caracterização do ciclo sono/vigília de professores do ensino médio em natal/rn

In the school environment is fundamental the knowledge about the sleep-wake cycle (SWC), because we find children and adolescents with excessive sleepiness and learning difficulties. Furthermore, teachers with high demand and with different work schedule, which may contribute to changes in SWC. The aim of this study was to describe the SWC of high school teachers in Natal/RN. Habits and knowledge about sleep, chronotype, SWC, daytime sleepiness, sleep quality and job satisfaction were described in 98 high school teachers from public and private school. These parameters were compared according to the characteristics of work, family structure and gender. Data collection was performed with the use of questionnaires in two stages: 1) "health and sleep" (general characterization of sleep habits), Horne & Ostberg questionnaire (characterization of chronotype), Epworth Sleepiness Scale and the Index of Pittsburg Sleep Quality, 2) The sleep diary for 14 days. From the results, we observe that the teachers woke up and went to bed earlier in the week and showed a reduction of time in bed around 42min comparing to weekend. This reduction in time in bed during the week was accompanied by an increase in nap duration on weekend. In addition the teachers woke up earlier on Saturdays than on Sundays, probably due to housework and leisure. The teachers' knowledge about sleep was low in relation to individual differences and effect of alcoholic beverages on sleep, and high in the consequences of sleep deprivation. The differences found in comparisons on the characteristics of work, family structure and gender were punctual, except concerning the work schedule. The teacher who started work in the morning and finished in the night, woke up earlier, went to bed later and had less time in bed, when compared to teachers who work only in two shifts. In addition, teachers with late chronotypes who begin the work in the morning had a greater irregularity in the wake up time compared to teachers with earlier and intermediate chronotypes. Half of teachers have excessive sleepiness, which was positive correlated with work dissatisfaction. In general, teachers showed IPSQ averages equivalent to poor sleep quality and the women showed worst averages. From the results, it is suggested that the SWC of teachers varies according to work schedule, leading to irregularity and partial sleep deprivation in the week, although these responses vary according to chronotype. These changes are accompanied by excessive daytime sleepiness and poor sleep quality. However, it is necessary to expand the sample to clarify the influence of variables related to work, family structure and gender together

Relação entre o ciclo sono e vigília e a função cardiorrespiratória em estudantes de medicina

Students, normally, present an irregular sleep pattern characterized by delays in sleep onset and offset from weekdays to weekends, short sleep duration on weekdays and long sleep duration on weekends. The reduction of the necessary sleep and the irregularity in the sleep patterns provoke relevant short- and long-term impairments on performances, for example, in cardiorespiratory function. The cardiorespiratory performance represents, in addition to fitness, traces associated to health conditions and in several studies to pattern and/or individual s sleep quality. The aim of this study was to evaluate the pattern of the sleep-wake cycle and the cardiorespiratory function of medical students under different class schedules. The study was accomplished with two classes of medical students of UFRN, one had classes at 7 am (n = 47) and the second had classes at 8 am (n = 41) during the week. On the first stage of the study all volunteers filled out an anamnesis, the International Physical Activity questionnaire, the Pittsburgh index of sleep quality, the Portuguese version of the Horne and Östberg cronotype questionnaire, the Health and Sleep questionnaire and the Epworth Scale of Somnolence (ESS). On the second stage, 24 students (12 of each class) had their activity rhythm monitored by actimeters set to record activity at a 2-min interval for 14 days concomitant to the completion of the sleep diary. In this same stage, each volunteer performed the effort test (treadmill) only once in the morning period (between 9:00 and 11:00). The students showed an irregular pattern of the sleep-wake cycle and this irregularity is strongly influenced by the class schedules, in addition to the contribution of the academic demand, social activities and endogenous factors. The students who woke up earlier showed greater irregularity in the sleep-wake pattern. The earlier was the class schedule the worse was the sleep quality and the greater was the frequency of students with excessive diurnal somnolence. The classes schedules and the irregular pattern of the sleep-wake cycle did not show effect on the cardiorespiratory performance of the medical students. The performance on the test seems to be affected by other factors, which can be related to the pattern of the sleep-wake cycle or not. Therefore, it is suggested that the late start of classes provokes less irregularity on the pattern of the sleep-wake cycle. However, it was observed that this irregularity and the class schedule seem not to affect the cardiorespiratory performance directly

Alterações do ciclo sono-vigília moduladas por Dopamina e suas consequências Mnemônicas

Neuroscience is on a rise of discoveries. Its wide interdisciplinary approach facilitates a more complex understanding of the brain, covering various areas in depth. However, many phenomena that fascinate human kind are far from being fully elucidated, such as the formation of memories and sleep. In this study we investigated the role of the dopaminergic system in the process of memory consolidation and modulation of the phases of sleep-wake cycle. We used two groups of animals: wildtype mice and hiperdopaminergic mice, heterozygous for the gene encoding the dopamine transporter protein. We observed in wild-type mice that the partial blockade of the D2 dopamine receptor by the drug haloperidol caused deficits in memory consolidation for object recognition, as well as a significant reduction in the duration of rapid eye movement sleep (REM). We also found a mnemonic deficit without pharmacological intervention in hiperdopaminergic animals; this deficit was reversed with haloperidol. The results suggest that dopamine plays a key role in memory consolidation for object recognition. The data also support a functional relationship between the dopaminergic system and the modulation of REM sleep

Caracterização do perfil do ciclo sono-vigília em ratos sob dessincronização forçada

The circadian behavior associated with the 24 hours light-dark (LD) cycle (T24) is due to a circadian clock , which in mammals is located in the hypothalamic suprachiasmatic nucleus (SCN). Under experimental conditions in which rats are espoused to a symmetric LD 22h cycle (T22) the two SCN regions, ventrolateral (vl) and dorsomedial (dm), can be functionally isolated, suggesting that each region regulates distinct physiological and behavioral components. The vl region regulates the locomotor activity and slow wave sleep (SWS) rhythms, while the dm region assures the body temperature and paradoxical sleep (PS) rhythms regulation. This research aimed to deepen the knowledge on the functional properties of circadian rhythmicity, specifically about the internal desynchronization process, and its consequences to locomotor activity and body temperature rhythms as well as to the sleep-wake cycle pattern in rats. We applied infrared motion sensors, implanted body temperature sensors and a telemetry system to record electrocorticogram (ECoG) and electromyogram (EMG) in two rat groups. The control group under 24h period LD cycle (T24: 12hL-12hD) to the baseline record and the experimental group under 22h period LD cycle (T22: 11hL- 11hD), in which is known to occur the uncoupling process of the circadian locomotor activity rhythm where the animals show two distinct locomotor activity rhythms: one synchronized to the external LD cycle, and another expressed in free running course, with period greater than 24h. As a result of 22h cycles, characteristic locomotor activity moment appear, that are coincidence moments (T22C) and non coincidence moments (T22NC) which were the main focus or our study. Our results show an increase in locomotor activity, especially in coincidence moments, and the inversion of locomotor activity, body temperature, and sleep-wake cycle patterns in non coincidence moments. We can also observe the increase in SWS and decrease in PS, both in coincidence and non coincidence moments. Probably the increases in locomotor activity as a way to promote the coupling between circadian oscillators generate an increased homeostatic pressure and thus increase SWS, promoting the decreasing in PS

Serotonin and circadian rhythms

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Measurement of melatonin in body fluids: Standards, protocols and procedures

Background and Purpose: The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6-sulfatoxymelatonin (a6MTs) in urine, is a defining feature of suprachiasmatic nucleus (SCN) function, the body's endogenous oscillatory pacemaker. The primary objective of this review is to ascertain the clinical benefits and limitations of current methodologies employed for detection and quantification of melatonin in biological fluids and tissues. Data Identification: A search of the English-language literature (Medline) and a systematic review of published articles were carried out. Study Selection: Articles that specified both the methodology for quantifying melatonin and indicated the clinical purpose were chosen for inclusion in the review. Data Extraction: The authors critically evaluated the methodological issues associated with various tools and techniques (e.g. standards, protocols, and procedures). Results of Data Synthesis: Melatonin measurements are useful for evaluating problems related to the onset or offset of sleep and for assessing phase delays or advances of rhythms in entrained individuals. They have also become an important tool for psychiatric diagnosis, their use being recommended for phase typing in patients suffering from sleep and mood disorders. Additionally, there has been a continuous interest in the use of melatonin as a marker for neoplasms of the pineal region. Melatonin decreases such as found with aging are or post pinealectomy can cause alterations in the sleep/wake cycle. The development of sensitive and selective methods for the precise detection of melatonin in tissues and fluids has increasingly been shown to have direct relevance for clinical decision making. Conclusions: Due to melatonin's low concentration, as well as the coexistence of numerous other compounds in the blood, the routine determination of melatonin has been an analytical challenge. The available evidence indicates however that these challenges can be overcome and consequently that evaluation of melatonin's presence and activity can be an accessible and useful tool for clinical diagnosis. © Springer-Verlag 2010.