- Email: [email protected]
205 EFFECTS OF ILEX PARAGUARIENSIS (YERBA MATE) ON SLEEP AND WAKEFULNESS
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
ing to the timing and method of sleep deprivation. Also, all experimental groups showed a decrease in pregnancy maintenance after preimplantation sleep deprivation of pregnant mice, indicating the importance of sleep in this period of life.
201
“COHERENCE” IN THE CORTICAL ELECTRICAL ACTIVITY DURING SLEEP AND WAKEFULNESS
S. Castro 1 , P. Torterolo 1 , A. Falconi 2 , L. Benedetto 1 , M. Gutierrez 1 . 1 UDELAR; UDERAR
2
Introduction: Sensory processing, motor activity, and cognitive function are sustained by cortical and subcortical networks, which are activated in a sequential or synchronized way. The interaction between two different cortical regions can be studied by detailed analysis of the electroencephalogram (EEG), using a mathematical algorithm called “coherence”. The coherence between different cortical regions reflects the strength of the interconnections between these areas. However, it is still not clear if and how the interactions among different cortical regions are affected by sleep and wakefulness states. Aim: To analyze the coherence among different cortical regions during active wakefulness, quiet wakefulness, REM sleep and slow wave sleep (SWS). Methods: Adult cats, chronically implanted with electrodes in different cortical regions were used for this study. The experiments were performed in cats because of their large cortical development (in comparison with rodents), and their consolidated waking and sleep states. Recordings were conducted for 4 hours, in semi-restrained conditions. Selected sections of the EEG recordings from different cortical areas in each behavioral state were analyzed using the “Spike 2” software. Coherence and correlations between pairs of EEG leads were estimated. The data were normalized by the Fisher z transform; thereafter, the significance of the differences among behavioral states was evaluated with the ANOVA and Fisher post hoc tests. The criterion chosen to discard the null hypothesis was P<0.05. Results: First, we determined the coherence and correlation between the somatosensory cortex and a visual unimodal association area. Our results show that although the correlation was higher during SWS, significantly higher coherence values were observed during REM sleep. This higher coherence was specific to the low frequency theta (4,5-8,5 Hz) and delta (0,5-4 Hz) bands. Conclusion: During REM sleep, when dreaming takes place in humans, the functional interactions between cortical regions increase. More data are needed in order to know if this fact is a global phenomenon, or if it is specific for interactions between specific cortical areas.
202
SLEEP DEPRIVATION DURING PREGNANCY AND BIOMETRIC ALTERATIONS IN MICE OFFSPRING
L. Fernandes, B.F.A. Calegare, S. Tufik, V. D’Almeida. UNIFESP Introduction: Growing interest has been driven by the discovery of a tight relationship between prenatal manipulations and development of short- and long-term health disorders. It is widely known that during pregnancy, twothirds of women consider their sleep to be abnormal. Moreover, several studies have shown that prenatal stress leads to weight alterations in offspring during development. Objectives: This study was undertaken to determine whether prenatal exposure to sleep deprivation alters weight and organs relative weight of offspring. Methods: One group of dams was continuously sleep deprived using the platform technique from gestational days 1 to 3 (PSD 72). Three additional groups were sleep deprived by gentle handling for six hours on gestational days 1 (GH 1), 2 (GH 2) or 3 (GH 3). Finally, to obtain a control group, a number of dams were allowed to sleep during the pregnancy. After birth, the offspring were weighed at Day 3 of life without gender separation. Within thirty days, the animals were classified as male and female. After, the offspring did not and after they did not suffer any other intervention during development until the third month of age when they were weighed and sacrificed for tissue collection (heart, fat, muscle and liver). Results: We observed an alteration in birth weight for pups whose mothers were sleep deprived by gentle handling compared with the control group. In groups GH 1 (2.79±0.31 g) and GH 3 (3.57±0.24 g), we observed a decrease in weight while group GH 2 (2.1±0.5 g) displayed an increase compared to the controls (2.51±0.28 g). However, by 3 months of age these differences disappeared. When gender was considered in the analysis we observed that
S55
adult females from the control group presented lower muscle relative mass (0.50% of total body weight) than male controls (0.64%). Conclusion: This data indicate that sleep deprivation of mothers in the beginning of pregnancy lead to birth biometric alterations in the offspring. Moreover, this difference was not maintained when animals reached adult life. Financial Support: AFIP, CNPq and FAPESP.
203
SPLEEN CELLULARITY IS ALTERED BY PARADOXAL SLEEP DEPRIVATION
L.D. Guariniello, M.D.B. Rodrigues, L. Lungato, V. D’Almeida, S. Tufik. UNIFESP The importance of adequate and appropriate sleep for health is widely recognized. However, evidence that sleep plays a role in immune competence is limited. Different deprivation schedules result in different immune outcomes, particularly in terms of leukocyte numbers and cell types. Thus, we asked whether paradoxal sleep deprivation (PSD) by the multiple platform method could modify a primary lymphoid organ, specifically the spleen. Naïve C57BL/6 mice were submitted to sleep deprivation for 72 hours with or without an additional sleep recovery (SR) period. Our data demonstrated that PSD promotes a significant decrease in the total spleen cellularity that returns to basal level after SR. Flow cytometry analysis showed no differences in the percentage of lymphocytes subpopulations or in numbers of NK1.1+ and F4/80+ cells. These findings suggest that sleep deprivation promotes a general cell loss that does not involve a specific immune population.
204
SLEEP DEPRIVATION INDUCES ALTERATIONS IN BONE MARROW AND THE PERIPHERAL BLOOD
L.D. Guariniello 1 , P. Vicari 2 , S. Tufik 1 . 1 UNIFESP; 2 AFIP The bone marrow compartment is the site of proliferation and maturation of multipotent stem cells into mature blood cells of different lineages. Noradrenergic innervation of the bone marrow is functionally dynamic and is responsive to generalized or immunological stress. Thus, the neural input of the sympathetic nervous system (SNS) to the bone marrow may be implicated in the regulation of hematopoiesis. Given that sleep deprivation can directly affect SNS, we asked whether paradoxical sleep deprivation (PSD) for 72 hours could modulate the hematopoietic compartments. Murine cellularity was analyzed in the bone marrow and peripheral blood of mice subjected to PSD with or without an additional sleep recovery (SR) period. Our data demonstrate that PSD promotes granulocytopenia and an increase of colonyforming units-granulocyte/macrophage (CFU-GM) in the bone marrow. Concomitantly, an increase of segment neutrophil cells and a decrease of lymphocytes were observed in the peripheral blood. These findings demonstrate that sleep deprivation may activate hematopoiesis and suggest its involvement in the cell migration process.
205
EFFECTS OF ILEX PARAGUARIENSIS (YERBA MATE) ON SLEEP AND WAKEFULNESS
M. Gutiérrez, L. Benedetto, P. Torterolo, A. Falconi. Facultad de Medicina, Uruguay Introduction: Every day, a variety of natural and artificial stimulant substances are commonly used in order to cope with daily activities. Ilex paraguariensis (Ip) consumed as an infusion, is the national drink of Argentina, Paraguay and Uruguay, and it is commonly used in Chile, Brazil and countries in the Middle East such as Syria and Lebanon. In addition, Ip has grown in popularity to encompass approximately 5% of the overall natural tea market in North America. Although a stimulant effect of this natural product is suggested by popular knowledge, there are not studies of the effects of Ip on wakefulness (W) and sleep. Aims. The aims of this work are to study: 1. The effects of Ip infusions on sleep and W parameters. 2. The effects of Ip administration on the sleep pressure triggered by sleep deprivation. Methods: Two adult cats were chronically implanted with electrodes for monitoring the behavioral states of sleep and W. Following oral delivery of an Ip solution (2.5 to 30%) or vehicle (distilled water), recording sessions were performed daily for 4 hours. In addition, another set of experimental sessions was conducted. A 4-hour sleep-deprivation paradigm was carried out by a somesthesic mild stimulus; after this period, the animals were allowed to
S56
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
sleep for another 2-hour period. The statistical significance of the difference between controls versus treatment effects on different sleep parameters was evaluated utilizing the Student’s t-test. The criterion chosen to discard the null hypothesis was P<0.05. Results: After the Ip infusion at 10% solution, there was an increase in the percentage of W (59.6±8.0) compared with controls (40.1±8.5, P<0.05). Additionally, there was a decrease in the percentage of slow wave sleep (31.4±4.4) compared with vehicle (47.3±4.5, P<0.05). The treatment did not significantly affect REM sleep. During the sleep deprivation period, there was a decrease in the number of activating stimulus after treatment with Ip solution in comparison with vehicle (22±1.2 Vs. 99.2±24.5, P<0.05). In addition, the physiological rebound after sleep deprivation was significantly reduced after the administration of Ip. The effects obtained were dose-dependant. Conclusions: In the present study we demonstrate that Ip increases W and reduces the pressure to sleep after sleep deprivation. Partially supported by a CSIC grant and Canarias SA.
206
RELATIONSHIP BETWEEN ADHD SCALES AND ELECTROENCEPHALOGRAPHIC ABNORMALITIES IN ATTENTION DEFICIT-HYPERACTIVITY DISORDER
in a double blind, randomized, crossover study. Administrations of modafinil or placebo to each subject were separated by a 2-week washout period. We measured TMS parameters, including resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), and short-interval intracortical inhibition (SICI) and facilitation (ICF). The parameters were measured before and three hours after a single dose of modafinil (400mg) or placebo administration and compared within and between patients and controls. Results: Drug-naïve narcolepsy patients had significantly increased CSP duration compared to normal controls (independent t-test, P<0.05), which suggests decreased excitability of cortical networks in human narcolepsy. Following modafinil administration, MEP amplitudes as well as SICI and ICF were increased, and CSP duration was shortened significantly in narcolepsy patients, indicating motor excitability was enhanced by modafinil. However, modafinil did not significantly change TMS parameters in normal subjects. In contrast, placebo administration did not alter any TMS parameter in both narcolepsy patients and normal subjects. Conclusions: Narcolepsy patients with cataplexy showed decreased cortical excitability compared to normal subjects. A single dose modafinil significantly increased motor excitability and shortened visual and auditory reaction times in narcolepsy patients but not in normal subjects.
H.J. Eun 1 , H.K. Kim 2 . 1 Jesus Hospital; 2 Jeongeup Asan Medical Center Background: Attention deficit-hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. It affects 3-5% of the school population, with a male-to-female ratio of 3 or 4 to 1. ADHD is a condition that often exhibits organic changes in the form of EEG abnormality. Both nonspecific and epileptiform abnormalities in the EEGs of children with ADHD have been reported. For epileptiform abnormalities, the reported incidence ranges from 6.1% to 30.1%. Objectives: This study aimed to analyze the relationship between scores on ADHD scales (ADHD diagnostic system; ADS, Korean version child behavior checklist [K-CBCL]) and EEG abnormalities in ADHD. Methods: We reviewed the medical records of thirty ADHD patients including boys (28) and girls (2) between 6 and 16 years. We analyzed their EEG, ADS and K-CBCL data. We recruited twenty-nine subjects to a control group composed of boys (13) and girls (16) between 6 and 16 years. We analyzed EEG, ADS and K-CBCL for members of the control group. Thereafter we compared and analyzed relationships among data from the control and ADHD patient groups, as well as ADHD scale (ADS, K-CBCL) differences between normal EEG and abnormal EEG in the ADHD group. Statistical analyses were performed with SPSS 12.0 for Windows. We applied the t-test for hypothesis testing. Results: The EEG abnormalities (epileptiform discharges and spikes) were 40% (12/30) in the ADHD group and 13.8% (4/29) in the control group. Subscales (inattention, impulsivity, response time, response time deviation) on the ADHD Diagnostic System (ADS) showed statistically significant differences between control and ADHD groups. Subscales (social subscale in social competence scale: withdrawn, somatic complaints, anxious/depressed, social problems, thought problems, attention problems, delinquent problems, aggressive behavior, internalizing problems, externalizing problems, total behavior problems on the behavior problem scale) of K-CBCL showed statistically significant differences, except some subscales of school and total social competence. But there were no statistical differences among scores on the ADS and K-CBCL scales between the abnormal and normal EEG subgroups in the ADHD patient group. Conclusion: ADHD patients showed more frequent EEG abnormalities than the control group. These findings suggest that ADHD patients have more frequent organic changes than control and that EEG abnormalities in the ADHD patient group have a limited ability to differentiate subtypes of ADHD.
208
V. Kahan 1 , D.A. Ribeiro 2 , M.L. Andersen 1 , T.A. Alvarenga 1 , S. Tufik 1 . Department of Psychobiology - Universidade Federal de São Paulo (UNIFESP), Brazil; 2 Biosciences - Universidade Federal de São Paulo (UNIFESP), Brazil
1
Objective: The aim of the present study was to measure the genetic damage induced by paradoxical sleep deprivation (PSD) in peripheral blood, heart, kidney, and liver tissues of three different male mice strains using the single cell gel (comet) assay. Materials and Methods: Ninety-day-old male Swiss, C57BL/6j and Hairless (HRS/j) mice were randomly distributed into two groups, home-cage control and sleep-deprived (SD). The experimental groups were submitted to SD for 72 h using the modified multiple platform method. After the experimental procedure, blood was collected and hearts, kidneys, and livers were immediately removed and minced in 0.9% NaCl. The supernatant was removed and the cellular suspensions (∼10 μl) were used for the single cell gel (comet) assay. A total of 50 randomly captured comets per animal were examined blindly at 400X magnification by one expert observer. The results obtained in the single cell gel (comet) assay were statistically evaluated using the Kruskal-Wallis non-parametric test followed by post-hoc Dunn’s test using Sigma Stat for Windows (Jadel Scientific, USA). Values are expressed as mean ± SEM. The level of significance was set at 5%. Results: In blood cells of the Swiss mouse strain, statistically significant differences in DNA damage were found compared to negative controls. By contrast, no significant differences in blood cell DNA damage were found in the C57BL/6j or Hairless (HRS/j) mice strains. Sleep deprivation resulted in extensive genotoxic effects in liver in the Swiss mouse strain. The hairless (HRS/j) and C57BL/j mouse strains did not show any signs of genotoxocity in this organ. The same lack of effect was noted in kidney and heart cells of all strains evaluated. Conclusion: Our results revealed that sleep deprivation resulted in genetic damage in the form of DNA breakage in blood and liver cells of the Swiss mouse strain only. Financial support: AFIP, FAPESP, CEPID e CNPq.
209 207
EFFECT OF MODAFINIL ON CORTICAL EXCITABILITY IN PATIENTS WITH NARCOLEPSY
S.B. Hong, E.Y. Joo, H.J. Kim, Y.H. Lim. Samsung Medical Center, Sungkyunkwan University School of Medicine Objective: To investigate the effect of modafinil on cortical excitability in human narcolepsy by trancranial magnetic stimulation (TMS). Methods: We recruited 19 drug-naïve narcolepsy patients with cataplexy (10 male, mean age 28.5 yrs) and 25 age- and sex-matched normal subjects. Patients and controls received a single dose of modafinil (400 mg) or placebo
SLEEP LOSS INDUCES DIFFERENTIAL RESPONSE RELATED TO GENOTOXICITY IN MULTIPLE ORGANS OF THREE DIFFERENT MICE STRAINS
REM SLEEP DEPRIVATION MODULATES TYROSINE HYDROXYLASE EXPRESSION: BEHAVIORAL AND MOLECULAR ALTERATIONS
M.M.S. Lima 1 , M.L. Andersen 2 , A.B. Reksidler 3 , M. Vital 3 , S. Tufik 2 . 1 UFSC; UNIFESP; 3 UFPR
2
Introduction: Dopamine (DA) is critically involved in regulating neural processes responsible for complex movements and emotions. Alterations in central dopaminergic neurotransmission have been implicated in important neurological and psychiatric disorders such as Parkinson’s disease (PD) and schizophrenia. In addition, DA has recently been recognized as fundamental in the regulation of sleep-wake states.
ing to the timing and method of sleep deprivation. Also, all experimental groups showed a decrease in pregnancy maintenance after preimplantation sleep deprivation of pregnant mice, indicating the importance of sleep in this period of life.
201
“COHERENCE” IN THE CORTICAL ELECTRICAL ACTIVITY DURING SLEEP AND WAKEFULNESS
S. Castro 1 , P. Torterolo 1 , A. Falconi 2 , L. Benedetto 1 , M. Gutierrez 1 . 1 UDELAR; UDERAR
2
Introduction: Sensory processing, motor activity, and cognitive function are sustained by cortical and subcortical networks, which are activated in a sequential or synchronized way. The interaction between two different cortical regions can be studied by detailed analysis of the electroencephalogram (EEG), using a mathematical algorithm called “coherence”. The coherence between different cortical regions reflects the strength of the interconnections between these areas. However, it is still not clear if and how the interactions among different cortical regions are affected by sleep and wakefulness states. Aim: To analyze the coherence among different cortical regions during active wakefulness, quiet wakefulness, REM sleep and slow wave sleep (SWS). Methods: Adult cats, chronically implanted with electrodes in different cortical regions were used for this study. The experiments were performed in cats because of their large cortical development (in comparison with rodents), and their consolidated waking and sleep states. Recordings were conducted for 4 hours, in semi-restrained conditions. Selected sections of the EEG recordings from different cortical areas in each behavioral state were analyzed using the “Spike 2” software. Coherence and correlations between pairs of EEG leads were estimated. The data were normalized by the Fisher z transform; thereafter, the significance of the differences among behavioral states was evaluated with the ANOVA and Fisher post hoc tests. The criterion chosen to discard the null hypothesis was P<0.05. Results: First, we determined the coherence and correlation between the somatosensory cortex and a visual unimodal association area. Our results show that although the correlation was higher during SWS, significantly higher coherence values were observed during REM sleep. This higher coherence was specific to the low frequency theta (4,5-8,5 Hz) and delta (0,5-4 Hz) bands. Conclusion: During REM sleep, when dreaming takes place in humans, the functional interactions between cortical regions increase. More data are needed in order to know if this fact is a global phenomenon, or if it is specific for interactions between specific cortical areas.
202
SLEEP DEPRIVATION DURING PREGNANCY AND BIOMETRIC ALTERATIONS IN MICE OFFSPRING
L. Fernandes, B.F.A. Calegare, S. Tufik, V. D’Almeida. UNIFESP Introduction: Growing interest has been driven by the discovery of a tight relationship between prenatal manipulations and development of short- and long-term health disorders. It is widely known that during pregnancy, twothirds of women consider their sleep to be abnormal. Moreover, several studies have shown that prenatal stress leads to weight alterations in offspring during development. Objectives: This study was undertaken to determine whether prenatal exposure to sleep deprivation alters weight and organs relative weight of offspring. Methods: One group of dams was continuously sleep deprived using the platform technique from gestational days 1 to 3 (PSD 72). Three additional groups were sleep deprived by gentle handling for six hours on gestational days 1 (GH 1), 2 (GH 2) or 3 (GH 3). Finally, to obtain a control group, a number of dams were allowed to sleep during the pregnancy. After birth, the offspring were weighed at Day 3 of life without gender separation. Within thirty days, the animals were classified as male and female. After, the offspring did not and after they did not suffer any other intervention during development until the third month of age when they were weighed and sacrificed for tissue collection (heart, fat, muscle and liver). Results: We observed an alteration in birth weight for pups whose mothers were sleep deprived by gentle handling compared with the control group. In groups GH 1 (2.79±0.31 g) and GH 3 (3.57±0.24 g), we observed a decrease in weight while group GH 2 (2.1±0.5 g) displayed an increase compared to the controls (2.51±0.28 g). However, by 3 months of age these differences disappeared. When gender was considered in the analysis we observed that
S55
adult females from the control group presented lower muscle relative mass (0.50% of total body weight) than male controls (0.64%). Conclusion: This data indicate that sleep deprivation of mothers in the beginning of pregnancy lead to birth biometric alterations in the offspring. Moreover, this difference was not maintained when animals reached adult life. Financial Support: AFIP, CNPq and FAPESP.
203
SPLEEN CELLULARITY IS ALTERED BY PARADOXAL SLEEP DEPRIVATION
L.D. Guariniello, M.D.B. Rodrigues, L. Lungato, V. D’Almeida, S. Tufik. UNIFESP The importance of adequate and appropriate sleep for health is widely recognized. However, evidence that sleep plays a role in immune competence is limited. Different deprivation schedules result in different immune outcomes, particularly in terms of leukocyte numbers and cell types. Thus, we asked whether paradoxal sleep deprivation (PSD) by the multiple platform method could modify a primary lymphoid organ, specifically the spleen. Naïve C57BL/6 mice were submitted to sleep deprivation for 72 hours with or without an additional sleep recovery (SR) period. Our data demonstrated that PSD promotes a significant decrease in the total spleen cellularity that returns to basal level after SR. Flow cytometry analysis showed no differences in the percentage of lymphocytes subpopulations or in numbers of NK1.1+ and F4/80+ cells. These findings suggest that sleep deprivation promotes a general cell loss that does not involve a specific immune population.
204
SLEEP DEPRIVATION INDUCES ALTERATIONS IN BONE MARROW AND THE PERIPHERAL BLOOD
L.D. Guariniello 1 , P. Vicari 2 , S. Tufik 1 . 1 UNIFESP; 2 AFIP The bone marrow compartment is the site of proliferation and maturation of multipotent stem cells into mature blood cells of different lineages. Noradrenergic innervation of the bone marrow is functionally dynamic and is responsive to generalized or immunological stress. Thus, the neural input of the sympathetic nervous system (SNS) to the bone marrow may be implicated in the regulation of hematopoiesis. Given that sleep deprivation can directly affect SNS, we asked whether paradoxical sleep deprivation (PSD) for 72 hours could modulate the hematopoietic compartments. Murine cellularity was analyzed in the bone marrow and peripheral blood of mice subjected to PSD with or without an additional sleep recovery (SR) period. Our data demonstrate that PSD promotes granulocytopenia and an increase of colonyforming units-granulocyte/macrophage (CFU-GM) in the bone marrow. Concomitantly, an increase of segment neutrophil cells and a decrease of lymphocytes were observed in the peripheral blood. These findings demonstrate that sleep deprivation may activate hematopoiesis and suggest its involvement in the cell migration process.
205
EFFECTS OF ILEX PARAGUARIENSIS (YERBA MATE) ON SLEEP AND WAKEFULNESS
M. Gutiérrez, L. Benedetto, P. Torterolo, A. Falconi. Facultad de Medicina, Uruguay Introduction: Every day, a variety of natural and artificial stimulant substances are commonly used in order to cope with daily activities. Ilex paraguariensis (Ip) consumed as an infusion, is the national drink of Argentina, Paraguay and Uruguay, and it is commonly used in Chile, Brazil and countries in the Middle East such as Syria and Lebanon. In addition, Ip has grown in popularity to encompass approximately 5% of the overall natural tea market in North America. Although a stimulant effect of this natural product is suggested by popular knowledge, there are not studies of the effects of Ip on wakefulness (W) and sleep. Aims. The aims of this work are to study: 1. The effects of Ip infusions on sleep and W parameters. 2. The effects of Ip administration on the sleep pressure triggered by sleep deprivation. Methods: Two adult cats were chronically implanted with electrodes for monitoring the behavioral states of sleep and W. Following oral delivery of an Ip solution (2.5 to 30%) or vehicle (distilled water), recording sessions were performed daily for 4 hours. In addition, another set of experimental sessions was conducted. A 4-hour sleep-deprivation paradigm was carried out by a somesthesic mild stimulus; after this period, the animals were allowed to
S56
Abstracts of 3rd International Congress of the Association of Sleep Medicine (WASM) / Sleep Medicine 10, Suppl. 2 (2009) S1–S83
sleep for another 2-hour period. The statistical significance of the difference between controls versus treatment effects on different sleep parameters was evaluated utilizing the Student’s t-test. The criterion chosen to discard the null hypothesis was P<0.05. Results: After the Ip infusion at 10% solution, there was an increase in the percentage of W (59.6±8.0) compared with controls (40.1±8.5, P<0.05). Additionally, there was a decrease in the percentage of slow wave sleep (31.4±4.4) compared with vehicle (47.3±4.5, P<0.05). The treatment did not significantly affect REM sleep. During the sleep deprivation period, there was a decrease in the number of activating stimulus after treatment with Ip solution in comparison with vehicle (22±1.2 Vs. 99.2±24.5, P<0.05). In addition, the physiological rebound after sleep deprivation was significantly reduced after the administration of Ip. The effects obtained were dose-dependant. Conclusions: In the present study we demonstrate that Ip increases W and reduces the pressure to sleep after sleep deprivation. Partially supported by a CSIC grant and Canarias SA.
206
RELATIONSHIP BETWEEN ADHD SCALES AND ELECTROENCEPHALOGRAPHIC ABNORMALITIES IN ATTENTION DEFICIT-HYPERACTIVITY DISORDER
in a double blind, randomized, crossover study. Administrations of modafinil or placebo to each subject were separated by a 2-week washout period. We measured TMS parameters, including resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), and short-interval intracortical inhibition (SICI) and facilitation (ICF). The parameters were measured before and three hours after a single dose of modafinil (400mg) or placebo administration and compared within and between patients and controls. Results: Drug-naïve narcolepsy patients had significantly increased CSP duration compared to normal controls (independent t-test, P<0.05), which suggests decreased excitability of cortical networks in human narcolepsy. Following modafinil administration, MEP amplitudes as well as SICI and ICF were increased, and CSP duration was shortened significantly in narcolepsy patients, indicating motor excitability was enhanced by modafinil. However, modafinil did not significantly change TMS parameters in normal subjects. In contrast, placebo administration did not alter any TMS parameter in both narcolepsy patients and normal subjects. Conclusions: Narcolepsy patients with cataplexy showed decreased cortical excitability compared to normal subjects. A single dose modafinil significantly increased motor excitability and shortened visual and auditory reaction times in narcolepsy patients but not in normal subjects.
H.J. Eun 1 , H.K. Kim 2 . 1 Jesus Hospital; 2 Jeongeup Asan Medical Center Background: Attention deficit-hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. It affects 3-5% of the school population, with a male-to-female ratio of 3 or 4 to 1. ADHD is a condition that often exhibits organic changes in the form of EEG abnormality. Both nonspecific and epileptiform abnormalities in the EEGs of children with ADHD have been reported. For epileptiform abnormalities, the reported incidence ranges from 6.1% to 30.1%. Objectives: This study aimed to analyze the relationship between scores on ADHD scales (ADHD diagnostic system; ADS, Korean version child behavior checklist [K-CBCL]) and EEG abnormalities in ADHD. Methods: We reviewed the medical records of thirty ADHD patients including boys (28) and girls (2) between 6 and 16 years. We analyzed their EEG, ADS and K-CBCL data. We recruited twenty-nine subjects to a control group composed of boys (13) and girls (16) between 6 and 16 years. We analyzed EEG, ADS and K-CBCL for members of the control group. Thereafter we compared and analyzed relationships among data from the control and ADHD patient groups, as well as ADHD scale (ADS, K-CBCL) differences between normal EEG and abnormal EEG in the ADHD group. Statistical analyses were performed with SPSS 12.0 for Windows. We applied the t-test for hypothesis testing. Results: The EEG abnormalities (epileptiform discharges and spikes) were 40% (12/30) in the ADHD group and 13.8% (4/29) in the control group. Subscales (inattention, impulsivity, response time, response time deviation) on the ADHD Diagnostic System (ADS) showed statistically significant differences between control and ADHD groups. Subscales (social subscale in social competence scale: withdrawn, somatic complaints, anxious/depressed, social problems, thought problems, attention problems, delinquent problems, aggressive behavior, internalizing problems, externalizing problems, total behavior problems on the behavior problem scale) of K-CBCL showed statistically significant differences, except some subscales of school and total social competence. But there were no statistical differences among scores on the ADS and K-CBCL scales between the abnormal and normal EEG subgroups in the ADHD patient group. Conclusion: ADHD patients showed more frequent EEG abnormalities than the control group. These findings suggest that ADHD patients have more frequent organic changes than control and that EEG abnormalities in the ADHD patient group have a limited ability to differentiate subtypes of ADHD.
208
V. Kahan 1 , D.A. Ribeiro 2 , M.L. Andersen 1 , T.A. Alvarenga 1 , S. Tufik 1 . Department of Psychobiology - Universidade Federal de São Paulo (UNIFESP), Brazil; 2 Biosciences - Universidade Federal de São Paulo (UNIFESP), Brazil
1
Objective: The aim of the present study was to measure the genetic damage induced by paradoxical sleep deprivation (PSD) in peripheral blood, heart, kidney, and liver tissues of three different male mice strains using the single cell gel (comet) assay. Materials and Methods: Ninety-day-old male Swiss, C57BL/6j and Hairless (HRS/j) mice were randomly distributed into two groups, home-cage control and sleep-deprived (SD). The experimental groups were submitted to SD for 72 h using the modified multiple platform method. After the experimental procedure, blood was collected and hearts, kidneys, and livers were immediately removed and minced in 0.9% NaCl. The supernatant was removed and the cellular suspensions (∼10 μl) were used for the single cell gel (comet) assay. A total of 50 randomly captured comets per animal were examined blindly at 400X magnification by one expert observer. The results obtained in the single cell gel (comet) assay were statistically evaluated using the Kruskal-Wallis non-parametric test followed by post-hoc Dunn’s test using Sigma Stat for Windows (Jadel Scientific, USA). Values are expressed as mean ± SEM. The level of significance was set at 5%. Results: In blood cells of the Swiss mouse strain, statistically significant differences in DNA damage were found compared to negative controls. By contrast, no significant differences in blood cell DNA damage were found in the C57BL/6j or Hairless (HRS/j) mice strains. Sleep deprivation resulted in extensive genotoxic effects in liver in the Swiss mouse strain. The hairless (HRS/j) and C57BL/j mouse strains did not show any signs of genotoxocity in this organ. The same lack of effect was noted in kidney and heart cells of all strains evaluated. Conclusion: Our results revealed that sleep deprivation resulted in genetic damage in the form of DNA breakage in blood and liver cells of the Swiss mouse strain only. Financial support: AFIP, FAPESP, CEPID e CNPq.
209 207
EFFECT OF MODAFINIL ON CORTICAL EXCITABILITY IN PATIENTS WITH NARCOLEPSY
S.B. Hong, E.Y. Joo, H.J. Kim, Y.H. Lim. Samsung Medical Center, Sungkyunkwan University School of Medicine Objective: To investigate the effect of modafinil on cortical excitability in human narcolepsy by trancranial magnetic stimulation (TMS). Methods: We recruited 19 drug-naïve narcolepsy patients with cataplexy (10 male, mean age 28.5 yrs) and 25 age- and sex-matched normal subjects. Patients and controls received a single dose of modafinil (400 mg) or placebo
SLEEP LOSS INDUCES DIFFERENTIAL RESPONSE RELATED TO GENOTOXICITY IN MULTIPLE ORGANS OF THREE DIFFERENT MICE STRAINS
REM SLEEP DEPRIVATION MODULATES TYROSINE HYDROXYLASE EXPRESSION: BEHAVIORAL AND MOLECULAR ALTERATIONS
M.M.S. Lima 1 , M.L. Andersen 2 , A.B. Reksidler 3 , M. Vital 3 , S. Tufik 2 . 1 UFSC; UNIFESP; 3 UFPR
2
Introduction: Dopamine (DA) is critically involved in regulating neural processes responsible for complex movements and emotions. Alterations in central dopaminergic neurotransmission have been implicated in important neurological and psychiatric disorders such as Parkinson’s disease (PD) and schizophrenia. In addition, DA has recently been recognized as fundamental in the regulation of sleep-wake states.