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

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Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83

light phase (the period during which rats sleep most) the PD group showed a significant reduction in sleep efficiency and total non-REM sleep time as well as an increase in the number of arousal events compared with control animals. In the dark period, the PD group also had lower sleep efficiency (day 7 to 28). REM sleep was only affected toward the end of the experimental period (day 21-28). Conclusion: Our results suggest that PD resulted in marked sleep disruption, especially in non-REM sleep, likely due to the development of orofacial pain.

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Accuracy of subjective sleep state perception

W.C. Shin, J.E. Yoon, E.J. Jang, M.J. Sung, H.K. Cha. Dept. of Neurology, KyungHee East-west Neo Medical Center, KyungHee University School of Medicine Introduction: In general, electrophysiologically measured sleep (using EEG) correlates quite well with subjective state perception. However, in some sleep disorders with insomnia and in sleep breathing disorder, there were some discrepancies between perceived and measured sleep. Objectives: To assess the accuracy of subjective perception about the previous night’s sleep and the factors affecting this perception. To this end we analyzed overnight polysomnography and asked subjects undergoing polysomnography about their subjective perception of sleep. Methods: We evaluated 175 patients who underwent overnight polysomnography. We assessed the habitual sleep pattern (total sleep time and sleep latency and awakening frequency during sleep) using a one week sleep log and several sleep questionnaires, such as Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS), Beck depression inventory (BDI), Insomnia Severity Index (ISI). After overnight polysomnography, we asked for their subjective perception of sleep latency and total sleep time during the previous night sleep. Results: Mean subjective sleep latency (SSL) was 29±35.1 minutes, subjective total sleep time (STST) 284±102.4 minutes, whereas objective sleep latency (OSL) and objective total sleep time (OTST), as with overnight polysomnography were 11.4±19.1 and 320.5±50.7, respectively. Only 17 patients (9.7%) reported shorter SSL than OSL. SSL was correlated with OSL (p=0.001) and inversely associated with OTST (p=0.001) and STST (p=0.001). STST were significantly correlated with OTST and negatively with SSL. Comparing the group with longer SSL than OSL and the group with shorter SSL than OSL, there were no differences in SSS, ESS, ISI, PSQI, BDI, sleep architectures and sleep efficacy as calculated with overnight polysomnography. The group with shorter SSL than OSL had higher apnea-hypopnea index and arousal index and lower oxygen saturation than group with longer SSL than OSL. Comparing with STST and OTST, there were significantly lower sleep efficacy and higher waking time after sleep onset in the group with shorter STST and longer STST than OTST. Conclusion: This study suggests that the most patients perceive sleep latency and total sleep time to be longer than the objectively recorded sleep latency and total sleep time. The patients with obstructive sleep apnea hypopnea syndrome usually sense sleep latency to be shorter than it actually was.

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GENDER DIFFERENCES IN SLEEP PATTERN OF RATS IN AN EXPERIMENTAL MODEL OF OSTEOARTHRITIS

A. Silva, M.L. Andersen, P. Araujo, A. Zager, S. Tufik. UNIFESP Introduction: Osteoarthritis (OA) is a major healthcare burden with increasing incidence, characterized by degeneration of articular cartilage. It is associated with chronic pain and sleep disturbance. Objective: The current study examined the long-term effect of chronic articular pain on sleep patterns in an experimental model of OA in females as compared to male rats. Methods: Rats were implanted with electrodes for electrocorticography and electromyography and assigned to control, sham or OA groups. OA was induced by the intra-articular administration of (2 mg) monosodium iodoacetate into the left knee joint in male and female (at estrus and diestrus phases) rats. Sleep was monitored at days 1, 10, 15, 20 and 28 after iodoacetate injection during light and dark periods. Results: The results showed that the sleep architecture changed in both genders. These alterations occurred in the light and dark period, and began on D1 and persisted until the end of the study. OA rats regardless of gender

showed a fragmented sleep pattern with reduced sleep efficiency, slow-wave sleep, and paradoxical sleep, as well as with fewer paradoxical sleep bouts. However, the males showed reduced sleep efficiency and slow-wave sleep in comparison to females in the dark period. Additionally, OA affected the hormonal levels in the male rats, as testosterone levels were reduced compared with the control and sham groups. In females, progesterone and estradiol remained unchanged during the study. Conclusion: Thus, our results suggest that the chronic model of OA influenced sleep patterns in both genders; however, males appear to be more affected. Support: Research supported by AFIP and FAPESP (CEPID #98/14303-3 to S.T. and #07/56620-6 to A.S.). Sergio Tufik and Monica Andersen are recipients of fellowships from CNPq.

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SLEEP PATTERN IN AN EXPERIMENTAL MODEL OF OSTEOARTHRITIS

A. Silva, M.L. Andersen, S. Tufik. UNIFESP Introduction: Osteoarthritis (OA) is a major healthcare burden of increasing prevalence. It has been demonstrated that the relationship between pain and sleep produces changes in sleep patterns and pain perception. However, electrophysiological studies in animal models of pain are limited. The current study examined the effect of chronic articular pain on sleep patterns in an experimental model of OA. Methods: Rats were implanted with electrodes for electrocorticography and electromyography. OA was induced in these rats by the intra-articular administration of monosodium iodoacetate into the left knee joint. Sleep recordings were monitored during light and dark periods lasting 12 h each and were evaluated at baseline as well as on days 1, 10, 15, 20 and 28 after iodoacetate injection or assignment to sham or control groups. The pain threshold was also assessed by hot plate testing in other groups of rats at the same time points. Results: The results demonstrated that OA significantly reduced the thermal pain threshold from day 10 until the end of the experiment. OA rats exhibited reduced sleep efficiency, slow wave sleep and paradoxical sleep and an increased number of microarousals during the light periods compared with baseline and with control and sham groups. These changes in sleep pattern occurred mostly between days 10 and 28. During the dark period, sleep disturbances were also characterized by decreased sleep efficiency, slow wave sleep, and paradoxical sleep, although sleep was only initially fragmented. Conclusion: Pain associated with the rat OA model caused alterations in sleep architecture by disrupting the sleep pattern. Support: Research supported by AFIP and FAPESP (CEPID #98/14303-3 to S.T. and #07/56620-6 to A.S.). Sergio Tufik and Monica Andersen are recipients of fellowships from CNPq.

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CHRONIC SLEEP RESTRICTION INDUCES CALCIUM SIGNALING ALTERATIONS IN THE CA3 HIPPOCAMPAL NEURONS OF AGED RATS

L. de Souza, S.S. Smaili, G.S. Lopes, R.P. Ureshino, M.L. Andersen, S. Tufik. UNIFESP Sleep deprivation affects many biological processes, including synaptic function and levels of many neurotransmitters. Calcium modulates many neural processes, including synaptic plasticity and apoptosis. However, the maintenance of low cytosolic Ca2+ levels is critical to cell survival. Mitochondria contribute to the maintenance of resting Ca2+ levels through the uptake of calcium from the cytosol into this organelle. Glutamate (GLUT), an important excitatory neurotransmitter, promotes Ca2+ influx to the cytosol of brain cells. Under certain circumstances, GLUT may cause a large and sustained increase in the intracellular Ca2+ , and other alterations that cause excitotoxicity. In the present work, we evaluated the effect of sleep restriction in the calcium signaling induced by GLUT or FCCP/Oligomycin in the hippocampus of aged rats. Two experiments were performed using 14 male Wistar rats (22-25 months old) divided in two groups: the sleep restriction group (SRG) and the control group (CG). The SR procedure (15 days) was based on submitting the animals to the platform for 18 h (4 h pm - 10 h am), with 6 h intervals, where they were allowed to sleep (10 h am - 4 h pm). The multiple platform technique was used for sleep deprivation. The CG was kept in their home-cages. Slices (200 μm) were obtained from the hippocampus by

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