Effects of REM sleep deprivation of ACTH-induced yawning

Central administration of ACTH in rats induces yawning and stretching. In order to study the effects of REM sleep deprivation on ACTH-induced yawning, the peptide was injected immediately after the REM sleep deprivation period or 24 h later. REM sleep deprivation impaired ACTH-induced yawning, but after a 24-hour recovery period, rats displayed a number of yawns similar to those in control animals. Implications for an involvement of dopaminergic and mainly cholinergic systems are discussed.     

REM sleep deprivation induces a decrease in norepinephrine-stimulated 3H-cyclic AMP accumulation in slices from rat brain

Beta adrenergic sites in rat brain are reduced after repeated treatment with antidepressant drugs, with REM sleep deprivation (REMSd) having the same effect. This paper reports the effects of REMSd in the production of 3H-cyclic AMP in frontal cortical slices by NE challenge. Data presented in this paper report a marked decrease in 3H-cyclic AMP synthesis after REMSd, which is in accordance with previous results showing adrenergic receptor down-regulation following REMSd. Results are discussed in view of possible interaction with dopaminergic systems and depression management.     

Paradoxical sleep deprivation facilitates subsequent corticosterone response to a mild stressor in rats

The pituitary-adrenal responsiveness to a mild stressor was assessed in rats that were deprived of paradoxical sleep (PS) and in controls that were not deprived. Animals were either individually- or group-deprived for 96 h and hormone levels were assessed at 0, 5, 20 or 60 min after a saline injection+novelty and compared with rats which were not deprived. Both types of PS deprivation resulted in elevated adrenocorticotropin levels at 0 min, which peaked at 5 min in all animals. Individually-deprived rats exhibited the highest corticosterone (CORT) levels at 0 min. Peak levels were higher and occurred earlier in PS-deprived than in control rats (5 vs. 20 min, respectively). At 20 min, CORT levels had already returned to unstressed levels in PS-deprived rats, but not in control rats. These data indicate that PS deprivation induces facilitation of the adrenocortical response to a mild stressor, but do not suggest that PS deprivation changes the negative feedback sensitivity to CORT.     

Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat

The instrumental methods to induce paradoxical sleep (PS) deprivation are stressful. The modified multiple platform method (MMPM), in which animals are placed with new cohorts inside the water tanks, results in augmented ACTH and corticosterone (CORT) responses. We hypothesised that this increased response could be attributed to social instability. In addition, we tested a new environmental control, a grid (GR) placed on the tank floor. Animals were submitted to the MMPM for 4 days as socially unstable (UG--coming from several cages) or stable groups (SG--coming from one cage), placed either on narrow platforms or on the grid. All UG animals presented higher ACTH levels than their SG counterparts, including home-cage controls. CORT levels of manipulated animals were higher than controls only in the stable group. UG animals presented heavier adrenals than their SG counterparts. Only adrenals from SG animals placed on the grid were similar to cage controls. SG rats lost less weight than UG animals. While UG animals ate the same amount of chow as home-cage controls, SG animals ate more than control and UG animals. These results suggest that the stress of the MMPM can be attenuated in stable groups. The introduction of a grid on the tank floor may serve an adequate environmental control as far as stress-related variables are considered.     

Pituitary-adrenal axis and behavioural responses of maternally deprived juvenile rats to the open field

Adult rats submitted to maternal deprivation (DEP) on post-natal day (pnd) 11 show smaller corticosterone (CORT) response to a saline injection than non-deprived (NDEP) rats, mainly at 30 days of age. In the present study we sought to investigate the pituitary-adrenal axis response of 30-day-old DEP rats to a 5-min open-field session, with lights and sound on. Hormone levels were assessed immediately or 20 min after the end of the stress, and were compared to basal levels. The immediate ACTH response of DEP females was the highest; this difference was no longer observed at 20 min, but hormone levels were still higher than basal. Both males and females showed an augmented CORT secretion immediately after the open field session, although only the response of NDEP females was higher than that of male counterparts. Moreover, DEP females showed a lower CORT response than their NDEP counterparts immediately after the stress. The CORT stress response remained equally elevated in males and females at the 20-min time point. Finally, DEP animals, regardless of the gender, ambulated more in the centre of the open field and displayed less grooming behaviour than NDEP pups, suggesting that DEP rats are less emotional than NDEP animals.     

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

The reproducibility of clinical OSA subtypes: a population-based longitudinal study

Purpose

The identification of subgroups of obstructive sleep apnea (OSA) is critical to understand disease outcome and treatment response and ultimately develop optimal care strategies customized for each subgroup. In this sense, we aimed to perform a cluster analysis to identify subgroups of individuals with OSA based on clinical parameters in the Epidemiological Sleep Study of São Paulo city (EPISONO). We aimed to analyze whether or not subgroups remain after 8 years, since there is not any evidence showing if these subtypes of clinical presentation of OSA in the same population can change overtime.

Methods

We used data derived from EPISONO cohort, which was followed over 8 years after baseline evaluation. All individuals underwent polysomnography, answered questionnaires, and had their blood collected for biochemical examinations. OSA was defined according to AHI?≥?15 events/h. Cluster analysis was performed using latent class analysis (LCA).

Results

Of the 1042 individuals in the EPISONO cohort, 68% agreed to participate in the follow-up study (n?=?712), and 704 were included in the analysis. We were able to replicate the OSA 3-cluster solution observed in previous studies: disturbed sleep, minimally symptomatic and excessively sleepy in both baseline (36%, 45% and 19%, respectively) and follow-up studies (42%, 43%, and 15%, respectively). The optimal cluster solution for our sample based on Bayesian information criterion (BIC) was 2 cluster for baseline (disturbed sleep and excessively sleepy) and 3 clusters for follow-up (disturbed sleep, minimally symptomatic, and excessively sleepy). A total of 45% of the participants migrated clusters between the two evaluations (and the factor associated with this was a greater delta-AHI (B?=????0.033, df?=?1, p?=?0.003).

Conclusions

The results replicate and confirm previously identified clinical clusters in OSA which remain in the longitudinal analysis, with some percentage of migration between clusters.