A retrospective study suggests that chronic insomnia behaves as a neurodegenerative disorder

© 2020 Neutel D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Insomnia is a prevalent sleep disorder. We examined chronic insomnia in terms of subjective and objective measures, according to self-reported duration of disorder. 443 patients were included from a sleep clinic diagnosed with chronic insomnia (ICSD3 criteria). Patients were retrospectively evaluated in terms of medical interview, sleep questionnaires, a standard polysomnography study, and subdivided in subgroups according to disorder duration. We compared patient’s results to a control group. Insomnia and control groups were significantly different in terms of TST, SE, SOL, N1 sleep, REM sleep, REM latency and number of REM episodes (p<0.05). For the group of ≤1 year of insomnia disorder all PSG parameters were statistically different from controls, except N2% and N3%, REM latency, and number of REM episodes. In the groups of 2 to 4 years, 10 to 19 years, and ≥ 20 years of insomnia we found the same differences except for REM sleep. On the contrary, in a subgroup analysis of 5 to 9 years of insomnia disorder duration, no differences to control group were found in TST, N1 or REM sleep to control group, adjusted for age. The polysomnographic sleep profile of chronic insomnia patients is different over time. It sketches an initial attempt of compensation in initial years of insomnia, which seems to disappear in long time chronic insomnia patients, as we usually see in others neurodegenerative disorders. Future studies are needed to clarify the natural history of chronic insomnia disorder and its behaviour as a neurodegenerative disorder.info:eu-repo/semantics/publishedVersio

Influence of food restriction on lipid profile and spontaneous glucose levels in male rats subjected to paradoxical sleep deprivation

OBJECTIVES: The purpose of this study was to determine the paired consequences of food restriction and paradoxical sleep deprivation on lipid profile and spontaneous glucose levels in male rats. METHOD: Food restriction began at weaning, with 6 g of food being provided per day, which was subsequently increased by 1 g per week until reaching 15 g per day by the eighth week. At adulthood, both rats subjected to food restriction and those fed ad libitum were exposed to paradoxical sleep deprivation for 96 h or were maintained in their home-cage groups. RESULTS: Animals subjected to food restriction exhibited a significant increase in high-density lipoprotein levels compared to animals that were given free access to food. After the paradoxical sleep deprivation period, the foodrestricted animals demonstrated reduced concentrations of high-density lipoprotein relative to their respective controls, although the values for the food-restricted animals after sleep deprivation were still higher than those for the ad libitum group. The concentration of low-density lipoproteins was significantly increased in sleep-deprived animals fed the ad libitum diet. The levels of triglycerides, very low-density lipoproteins, and glucose in foodrestricted animals were each decreased compared to both ad libitum groups. CONCLUSION: These results may help to illustrate the mechanisms underlying the relationship between sleep curtailment and metabolism and may suggest that, regardless of sleep deprivation, dietary restriction can minimize alterations in parameters related to cardiovascular risk.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Associacao Fundo de Incentivo a Pesquisa (AFIP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-CEPID)Universidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUNIFESP, Depto. de Psicobiologia98/14303-311/12325-6 e 10/14768-0SciEL

Influence of food restriction on lipid profile and spontaneous glucose levels in male rats subjected to paradoxical sleep deprivation

OBJECTIVES: The purpose of this study was to determine the paired consequences of food restriction and paradoxical sleep deprivation on lipid profile and spontaneous glucose levels in male rats. METHOD: Food restriction began at weaning, with 6 g of food being provided per day, which was subsequently increased by 1 g per week until reaching 15 g per day by the eighth week. At adulthood, both rats subjected to food restriction and those fed ad libitum were exposed to paradoxical sleep deprivation for 96 h or were maintained in their home-cage groups. RESULTS: Animals subjected to food restriction exhibited a significant increase in high-density lipoprotein levels compared to animals that were given free access to food. After the paradoxical sleep deprivation period, the foodrestricted animals demonstrated reduced concentrations of high-density lipoprotein relative to their respective controls, although the values for the food-restricted animals after sleep deprivation were still higher than those for the ad libitum group. The concentration of low-density lipoproteins was significantly increased in sleep-deprived animals fed the ad libitum diet. The levels of triglycerides, very low-density lipoproteins, and glucose in foodrestricted animals were each decreased compared to both ad libitum groups. CONCLUSION: These results may help to illustrate the mechanisms underlying the relationship between sleep curtailment and metabolism and may suggest that, regardless of sleep deprivation, dietary restriction can minimize alterations in parameters related to cardiovascular risk

Gender-related demographic, polysomnographic, cognitive and psychological factors in insomnia

info:eu-repo/semantics/publishedVersio

Validation of commonly used reference genes for sleep-related gene expression studies

<p>Abstract</p> <p>Background</p> <p>Sleep is a restorative process and is essential for maintenance of mental and physical health. In an attempt to understand the complexity of sleep, multidisciplinary strategies, including genetic approaches, have been applied to sleep research. Although quantitative real time PCR has been used in previous sleep-related gene expression studies, proper validation of reference genes is currently lacking. Thus, we examined the effect of total or paradoxical sleep deprivation (TSD or PSD) on the expression stability of the following frequently used reference genes in brain and blood: <it>beta-actin (b-actin), beta-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH)</it>, and <it>hypoxanthine guanine phosphoribosyl transferase (HPRT)</it>.</p> <p>Results</p> <p>Neither TSD nor PSD affected the expression stability of all tested genes in both tissues indicating that <it>b-actin, B2M, GAPDH </it>and <it>HPRT </it>are appropriate reference genes for the sleep-related gene expression studies. In order to further verify these results, the relative expression of <it>brain derived neurotrophic factor (BDNF) </it>and <it>glycerol-3-phosphate dehydrogenase1 (GPD1) </it>was evaluated in brain and blood, respectively. The normalization with each of four reference genes produced similar pattern of expression in control and sleep deprived rats, but subtle differences in the magnitude of expression fold change were observed which might affect the statistical significance.</p> <p>Conclusion</p> <p>This study demonstrated that sleep deprivation does not alter the expression stability of commonly used reference genes in brain and blood. Nonetheless, the use of multiple reference genes in quantitative RT-PCR is required for the accurate results.</p

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats

OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Associacao Fundo de Incentivo a Pesquisa (AFIP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (CEPID)Universidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUniversidade Federal de São Paulo (UNIFESP) Departamento BiocienciaUNIFESP, Depto. de PsicobiologiaUNIFESP, Depto. Biociencia98/14303-3 e 11/12325-6 e 10/50129-1 e 07/01228-4 e 09/03360-2SciEL

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats

OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Effects of sleep loss on reproductive function of male rats

It has been reported that copulatory experience may actually alter sexual performance in male rats. But indicating experience is a risky proposition since the statement is made in the absence of an established hormonal basis and number of copulations that define sexual experience condition. And also, the associated hormonal alterations observed in sexually high performing rats could have been caused by factors other than experience, such as sleep deprivation (SD). Whether it is trading sleep time for leisure time or for work, the shortage of sleep in present day society may lead to adverse alterations in body functions, even in the endocrine system, prompting changes sexual behavior and therefore, in reproductive function. In light of such considerations the current stage of the overall investigation forks into 2 studies: Study 1 seeks to determine the required time for the rat to acquire sexual experience as well as the hormonal profile of sexually active and sexually naïve rats. Study 2 examines the influence of sleep shortage upon sexual behavior (SB), hormonal profile, and spermatic parameters in sexually experienced rats. In Study 1 male rats underwent SB training in the presence of receptive females every other day over a nineday period. Results show that throughout this period 42.5% of the subjects displayed excellent sexual performance, 17.5% had adequate performance, 7.5% had low sexual activity and an unexpected 32.5% showed no sexual response at all. The hormonal analysis that followed showed that, when compared to subjects with adequate/excellent performance, the progesterone concentrations in the rats whose sexual performance was low or nil were decreased, as were those of testosterone. In Study 2 sexually experienced subjects underwent to a PSD protocol for 96h (PSD96h) and a sleep restriction protocol for 21 consecutive days (SR21d). In the latter, subjects experienced 18h of sleep deprivation followed by 6h in their home cages. Control groups (CTRL) remained in their home cages throughout the entire protocol. SB, hormonal profile and sperm analysis were assessed and it was found that PSD96h reduced sexual performance but SR21d did not alter SB in the rat subjects when compared to CTRL. As for hormonal alterations, the subjects submitted to PSD96h experienced a reduction in their levels of testosterone but no alterations occurred in the concentrations of progesterone, LH, and FSH. As for the semen analysis, both groups (PSD96h and SR21d), presented lower spermatic viability in relation to the CTRL. However, the loss of live spermatozoids was more pronounced in the PSD96h group than in the SR21d group. Taken together, the findings herein indicate that in addition to testosterone, progesterone is also a limiting factor in the sexual performance of male rats. And furthermore, that when submitted to PSD96h, rat subjects with excellent sexual activity loose sexual performance and also, they experience loss of spermatic viability as well as suffer decreases in testosterone concentrations. Likewise, there were also detrimental effects in the percentage of live spermatozoids in the SR21d subjects. The current study thus indicates that in order to maintain adequate sexual response an ideal concentration of not only testosterone but of the typically female hormone progesterone is also required. And also, regardless of the concentrations of one or another hormone involved in the cascade of events leading to spermatozoid formation, lack of sleep can be singled out as a detrimental factor in the reproductive function of male rats.Tem sido documentado que a experiência copulatória pode alterar o desempenho sexual em ratos machos. No entanto, as bases hormonais e o número de cópulas necessárias para o rato adquirir experiência sexual ainda não estão claramente estabelecidos. Por outro lado, as alterações hormonais podem ser resultantes de diversos fatores, em especial a falta de sono. A diminuição do tempo de sono presente na sociedade atual quer seja pelo excesso de trabalho ou até mesmo a troca do tempo de sono por momentos de lazer, pode levar ao comprometimento de diversas funções do nosso organismo, em especial o bom funcionamento do sistema endócrino que pode acarretar em prejuízos no comportamento sexual e consequentemente na função reprodutiva. Neste sentido, a presente etapa se divide em 2 estudos: no Artigo 1 determinamos o tempo necessário para o rato adquirir experiência sexual bem como o perfil hormonal de ratos sexualmente ativos e inexperientes. No Artigo 2 avaliamos a influência da falta de sono no comportamento sexual (CS), perfil hormonal e parâmetros espermáticos em ratos sexualmente experientes. Para a realização do Artigo 1, ratos machos foram submetidos ao treino de CS na presença de fêmeas receptivas durante 9 dias intercalados. Os resultados indicaram que durante esse período, 42,5% dos animais apresentaram excelente desempenho sexual, 17,5% mostraram um desempenho adequado, 7,5% tiveram baixa atividade e inesperadamente 32,5% dos animais não apresentaram nenhuma resposta sexual. Em relação aos resultados hormonais, os ratos com baixo/nenhum desempenho apresentaram menores concentrações de progesterona comparadas aos animais de excelente/adequado desempenho. A testosterona, por sua vez, foi significativamente reduzida nos animais de baixa/nenhuma atividade comparados com os animais de excelente/adequado desempenho. No Artigo 2, os ratos sexualmente ativos foram submetidos à privação de sono paradoxal durante 96 horas (PSP96h) ou a restrição de sono por 21 dias consecutivos (RS21d) que consiste em expor os animais a PSP por 18 horas e as 6 horas restantes deixá-los na gaiola moradia. Os grupos controles (CTRL) foram mantidos em gaiola de moradia durante todo o experimento. Em seguida foram avaliados o CS, o perfil hormonal e também o espermograma desses animais. Verificou-se que a PSP 96h foi capaz de diminuir o desempenho sexual. Entretanto, a RS21d não alterou o CS dos ratos em relação ao grupo CTRL. Quanto às alterações hormonais, os ratos submetidos à PSP 96h tiveram uma diminuição das concentrações de testosterona. A progesterona, LH e FSH não apresentaram nenhuma alteração significativa após os protocolos de falta de sono. Em relação à análise do sêmen, tanto o grupo PSP 96h como o grupo RS21d apresentaram uma menor viabilidade espermática em relação ao grupo CTRL. No entanto, a diminuição dos espermatozóides vivos foi mais acentuada no grupo PSP 96h do que no grupo RS21d. Tomados em conjunto, os achados do presente estudo indicam que além da testosterona, a progesterona também é um fator limitante para o bom desempenho dos ratos machos. Além disso, os animais com excelente atividade sexual, quando submetidos à PSP, apresentaram uma diminuição do desempenho sexual, da viabilidade espermática e ainda das concentrações de testosterona. Similarmente, os animais que foram restritos de sono, também tiveram comprometimento na porcentagem de espermatozóides vivos. Assim, nossos resultados sugerem que para manter uma resposta sexual adequada é necessária concentrações ideais não só de testosterona, mas também do hormônio tipicamente feminino, a progesterona. Ainda, independente das concentrações hormonais envolvidas na cascata de formação dos espermatozóides, a falta de sono prejudica a função reprodutiva de ratos machos.TEDESão Paulo, Escola Paulista de Medicina (EPM