Contributions to the understanding of the role of sleep on male sexual function

Penile erection is essential for successful reproduction, and depends on the integration of various mechanisms, including psychological, vascular, endocrine, neurological, and myogenic processes triggered by reflex response or psychogenic stimulus from central origin. During sleep, erections can occur through the descending pathway that passes through the spinal cord and signals able to activate the penile reflex system in all healthy males from birth to aging, regardless of the content of the dream. The cumulative duration of tumescence during the night is approximately 90 minutes or 20% of total sleep time. Since its discovery in the 1940s, the function of penile erection during sleep remains a puzzling enigma. It is important to note that elucidation of erectile mechanisms related to sleep and wakefulness is essential to the eventual diagnosis and treatment of impotence. Study of the interaction between the underlying neurobiological and neuroendocrine bases for sleep and sexual behavior in rats will illuminate the influence of hormonal factors in expression of mating behavior and its relationship with sleep. Although sleep is essential for good health, sleep loss is increasingly prevalent in the contemporary world. Sleep debt causes numerous changes to overall welfare. In fact, most of sleep deprivation in modern life occurs during paradoxical/ REM sleep in the second half of the night. However, the consequences of paradoxical sleep deprivation (PSD) on sexual function have been little studied. Thus, this thesis presents the main studies of the research on the role of sleep in sexual response. During the past 13 years, our work has revealed a marked participation of sleep, and especially its deprivation in male sexual function. To broaden the understanding of the complex interactions underlying the regulation of sexual behavior, we used two approaches: a) male rats submitted to PSD and then behavioral observation and hormonal analysis; or b) clinical studies including men with complaints of sexual dysfunction. The results have consistently shown that PSD has facilitates the occurrence of spontaneous genital reflexes in young, adult, and old rats. However, PSD promotes impairment of sexual performance in the presence of females. Herein, increased progesterone and decreased testosterone levels were documented in sleep deprived rats. The importance of this study to the scientific field is reflected by 112 citations of this original article. In the next experiments, we developed several protocols in order to identify hormonal factors modulated by PSD relevant to promoting good sexual response in male rats. We observed that administration of progesterone after PSD in castrated rats induced an increase in number of erections compared to rats administered testosterone, whereas pre-treatment with the progesterone receptor antagonist significantly reduced the number of erections after sleep deprivation. These results add more evidence to the participation of progesterone in core reproductive events, such as the erection. Regarding clinical findings derived from an epidemiological study, we observed an association between some polymorphisms related to erectile dysfunction complaints and sleep disorders. The line of research initiated in the PhD dissertation of the candidate provided ample evidence for a strong association between reduced sleep and changes in sexual function in male rats and men. Collectively, this thesis presents the main contributions of the candidate to the international literature on the topic of the role of sleep in male sexual function under a translational approach. Thus, it is possible to raise different perspectives to be used for pre-clinical and population studies: a) animal models incorporating different sophisticated methodologies to record penile erection during sleep deprivation; and b) conducting epidemiological studies with polysomnography to identify correlates of complaints of sexual dysfunction related to sleep disturbances. The impact of these studies together with the level of productivity in the scientific field enable us to maintain the excellence of our research group in the topic of "sleep and sexual behavior".A ereção peniana é essencial para o sucesso da reprodução e depende da integração de diversos mecanismos, como, por exemplo, psicológicos, vasculares, endócrinos, neurológicos e miogênicos, desencadeados por resposta reflexa ou estímulo psicogênico de origem central. Durante o sono, as ereções podem ocorrer por meio da via descendente, que passa pela medula espinhal, e envia impulsos capazes de ativar o sistema reflexo peniano em todos os homens saudáveis desde o nascimento até o envelhecimento, independentemente do conteúdo do sonho. O tempo de intumescimento durante esse período é de aproximadamente 90 minutos por noite ou 20% do tempo total de sono. Desde sua descoberta na década de 40, a função do intumescimento peniano durante o sono ainda permanece um enigma intrigante. Ressalta-se que a elucidação dos mecanismos eréteis relacionados ao sono e à vigília é essencial para o eventual diagnóstico e tratamento da impotência. Em ratos, o estudo da interação das bases neuroendócrinas do comportamento sexual e da neurobiologia do sono pode permitir a demonstração da influência dos fatores hormonais como determinantes da expressão global da atividade copulatória e sua relação com o sono. Embora o sono seja fundamental para a qualidade de vida, é cada vez mais prevalente a redução do tempo de sono no mundo contemporâneo. O débito de sono ocasiona inúmeras alterações na saúde. Dessa forma, para tentar investigar a importância do sono e como sua falta pode modular as funções biológicas, diferentes metodologias experimentais vêm sendo utilizadas, dentre elas a privação de sono paradoxal (PSP). De fato, no modo de vida atual, a maior parte da privação de sono ocorre na fase de sono paradoxal/REM, na segunda metade da noite. Assim, nesta tese apresentam-se os principais estudos da linha de pesquisa sobre o entendimento do sono sobre a resposta sexual. Durante os últimos 13 anos, nossos trabalhos têm revelado uma marcante participação do sono, e principalmente da sua privação, na função sexual masculina. Diferentes manipulações experimentais foram executadas na tentativa de ampliar a compreensão das interações complexas subjacentes à regulação do comportamento sexual. Para tanto, utilizou-se duas abordagens: a) ratos machos submetidos à PSP e em seguida à observação comportamental e à análise hormonal; ou b) estudos clínicos com homens com queixas de disfunção sexual. Os resultados têm consistentemente demonstrado que a PSP apresenta um efeito facilitatório sobre a ocorrência de reflexos genitais espontâneos em ratos jovens, adultos e idosos. No entanto, a PSP promove prejuízos no desempenho sexual na presença de fêmeas. Documentamos o aumento de progesterona e a redução de testosterona nos ratos privados de sono. A importância desse estudo no cenário científico reflete-se pelas 112 citações do artigo original. A partir desses achados, desenvolvemos diversos trabalhos no intuito de verificar os fatores hormonais relevantes para promover uma boa resposta sexual modulada pela PSP em ratos machos. Observamos que a administração de progesterona após a PSP em ratos castrados induziu um aumento no número de ereções em relação aos ratos administrados com testosterona, enquanto o pré-tratamento com antagonista do receptor de progesterona reduziu significativamente o número de ereções após privação de sono. Acreditamos que os resultados obtidos possam de alguma maneira adicionar mais subsídios para a marcante participação da progesterona em eventos essenciais da reprodução, como a ereção. No que concerne os achados clínicos derivados de um estudo epidemiológico, observou-se a relação de alguns polimorfismos com a queixa de disfunção erétil associada ou não com distúrbios de sono. Nesse contexto, a linha de pesquisa iniciada na tese de Doutorado da candidata tem revelado diversas evidências para uma forte associação entre a redução de sono e modificações na função sexual em ratos machos e em homens. Em conjunto, esta tese apresenta as principais contribuições da candidata sobre os estudos do papel do sono na função sexual masculina no âmbito translacional para a literatura internacional. Com isso, pode-se levantar diferentes perspectivas para essa temática tanto para abordagem pré-clínica como populacional: a) modelos animais que englobem diferentes metodologias sofisticadas de registro de ereção peniana durante a privação de sono; e b) condução de estudos epidemiológicos com polissonografia para identificação de correlatos de queixas de disfunção sexual com problemas de sono. O reflexo desses estudos em conjunto com esse nível de produção no cenário científico nos permitirá manter a excelência do nosso grupo nas pesquisas no tema “sono e comportamento sexual”.Associação Fundo de Incentivo à Pesquisa (AFIP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Auxílio aos Docentes e Alunos (FADA

Interactions between sleep, stress, and metabolism: From physiological to pathological conditions

AbstractPoor sleep quality due to sleep disorders and sleep loss is highly prevalent in the modern society. Underlying mechanisms show that stress is involved in the relationship between sleep and metabolism through hypothalamic–pituitary–adrenal (HPA) axis activation. Sleep deprivation and sleep disorders are associated with maladaptive changes in the HPA axis, leading to neuroendocrine dysregulation. Excess of glucocorticoids increase glucose and insulin and decrease adiponectin levels. Thus, this review provides overall view of the relationship between sleep, stress, and metabolism from basic physiology to pathological conditions, highlighting effective treatments for metabolic disturbances

Is sleep related to cancer in murine models of obstructive sleep disorder?

Universidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilWeb of Scienc

Does sleep deprivation and morphine influence wound healing?

The contrast between present-day sleep habits and those of the pre-industrial era are quite evident. One study recent has shown that the amount of sleep has decreased 2 h per night over the past 50 years. Such sleep curtailment, ubiquitous in the modern lifestyle, inflicts adverse repercussions upon health and well being. Investigations examining the relationship between stress and the skin have shown that different types of stress affect the healing process. Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process. Therefore, our hypothesis is that the lack of sleep associated with chronic treatment with morphine is detrimental to the healing of the skin in the animal model we have adopted. Thus, it is important that future studies consider the paradigm of sleep curtailment when investigating the mechanisms involved in the process of skin healing in individuals who are dependent on morphine. (C) 2011 Elsevier B.V. All rights reserved.Associacao Fundo de Incentivo a Pesquisa (AFIP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Dermatol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Dermatol, BR-04024002 São Paulo, BrazilFAPESP: 98/14303-3Web of Scienc

Wound-healing and benzodiazepines: does sleep play a role in this relationship?

Patients who have suffered burns frequently experience psychological consequences, among which anxiety disorders are prominent. Benzodiazepines are commonly administered to treat these symptoms. The effects of benzodiazepines on healing may not be direct but rather are modulated by alterations of the sleep architecture. This hypothesis is supported by studies that demonstrate the effects of benzodiazepines on the immune system and the inflammatory profile under both normal sleep conditions and during sleep deprivation, particularly rapid eye movement sleep deprivation.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)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP (CEPID)Universidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUNIFESP, Depto. de Psicobiologia2011/14462-0 e 2010/14768-098/14303-3SciEL

Impact of sex on hyperalgesia induced by sleep loss

This study evaluated the impact of sex on the short term consequences of different periods of sleep deprivation and the effect of the respective sleep recovery periods on nociceptive responses. Male and female C57BL/6J mice were assigned to the following groups: paradoxical sleep deprived (PSD) for 72 h, sleep restricted (SR) for 15 days, exposed to respective recovery periods for 24 h, or untreated home-cage controls (CTRL). Mice were submitted to a noxious thermal stimulus to evaluate their nociceptive response after PSD, SR, or recovery periods. Blood was collected for hormonal analysis. the nociceptive response was significantly lower in PSD and SR mice compared to CTRL animals, regardless of the sex. However, SR females had a lower paw withdrawal threshold than males. Sleep recovery was able to restore normal nociceptive sensitivity after PSD in both sexes. the hyperalgesia induced by SR was not reversed by sleep rebound. in females, low concentrations of estradiol were found after SR, and these concentrations continued to decrease after 24 hours of sleep recovery. the PSD male mice exhibited higher concentrations of corticosterone than the CTRL and SR male mice. Corticosterone levels were not affected by SR. Our study revealed that PSD and SR induce hyperalgesia in mice. the SR groups showed marked changes in the nociceptive response, and the females were more sensitive to these alterations. This finding indicates that, although different periods of sleep deprivation change the nociceptive sensitivity in male and female mice, sex could influence hyperalgesia induced by chronic sleep loss. (C) 2010 Elsevier Inc. All rights reserved.Associacao Fundo de Incentivo a Psicofarmacologia (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniv Fed Goias, Dept Ciencias Fisiol, Goiania, Go, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilFAPESP: 98/14303-3FAPESP: 10/50130-0Web of Scienc

Wound-healing and benzodiazepines: does sleep play a role in this relationship?

Patients who have suffered burns frequently experience psychological consequences, among which anxiety disorders are prominent. Benzodiazepines are commonly administered to treat these symptoms. The effects of benzodiazepines on healing may not be direct but rather are modulated by alterations of the sleep architecture. This hypothesis is supported by studies that demonstrate the effects of benzodiazepines on the immune system and the inflammatory profile under both normal sleep conditions and during sleep deprivation, particularly rapid eye movement sleep deprivation

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

Does Sleep Play a Role in the Relationship Among Depression, Anxiety, and Mortality in Lung Transplanted Patients?

Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilWeb of Scienc