Neuroendocrine and Peptidergic Regulation of Stress-Induced REM Sleep Rebound

Sleep homeostasis depends on the length and quality (occurrence of stressful events, for instance) of the preceding waking time. Forced wakefulness (sleep deprivation or sleep restriction) is one of the main tools used for the understanding of mechanisms that play a role in homeostatic processes involved in sleep regulation and their interrelations. Interestingly, forced wakefulness for periods longer than 24 h activates stress response systems, whereas stressful events impact on sleep pattern. Hypothalamic peptides (corticotropin-releasing hormone, prolactin, and the CLIP/ACTH (18-39)) play an important role in the expression of stress-induced sleep effects, essentially by modulating rapid eye movement sleep, which has been claimed to affect the organism resilience to the deleterious effects of stress. Some of the mechanisms involved in the generation and regulation of sleep and the main peptides/hypothalamic hormones involved in these responses will be discussed in this review.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/Centros de Pesquisa, Inovação e Difusão (CEPID)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Ibirapuera, Psychosomat Res Grp, Dept Psychol, Sao Paulo, BrazilUniv Ibirapuera, Psychosomat Res Grp, Dept Pharm, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Psychobiol, Sao Paulo, BrazilDepartment of Psychobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilFAPESP/CEPID: 98/14303-3CNPq: 486769/2013-5FAPESP: 2010/09087-3CNPq: 302294/2012-0FAPESP: 2015/26364-4Web of Scienc

Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH) impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM) and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation

REM Sleep Rebound as an Adaptive Response to Stressful Situations

Stress and sleep are related to each other in a bidirectional way. If on one hand poor or inadequate sleep exacerbates emotional, behavioral, and stress-related responses, on the other hand acute stress induces sleep rebound, most likely as a way to cope with the adverse stimuli. Chronic, as opposed to acute, stress impairs sleep and has been claimed to be one of the triggering factors of emotional-related sleep disorders, such as insomnia, depressive- and anxiety-disorders. These outcomes are dependent on individual psychobiological characteristics, conferring even more complexity to the stress-sleep relationship. Its neurobiology has only recently begun to be explored, through animal models, which are also valuable for the development of potential therapeutic agents and preventive actions. This review seeks to present data on the effects of stress on sleep and the different approaches used to study this relationship as well as possible neurobiological underpinnings and mechanisms involved. The results of numerous studies in humans and animals indicate that increased sleep, especially the rapid eye movement phase, following a stressful situation is an important adaptive behavior for recovery. However, this endogenous advantage appears to be impaired in human beings and rodent strains that exhibit high levels of anxiety and anxiety-like behavior

Role of Corticosterone on Sleep Homeostasis Induced by REM Sleep Deprivation in Rats

Sleep is regulated by humoral and homeostatic processes. If on one hand chronic elevation of stress hormones impair sleep, on the other hand, rapid eye movement (REM) sleep deprivation induces elevation of glucocorticoids and time of REM sleep during the recovery period. in the present study we sought to examine whether manipulations of corticosterone levels during REM sleep deprivation would alter the subsequent sleep rebound. Adult male Wistar rats were fit with electrodes for sleep monitoring and submitted to four days of REM sleep deprivation under repeated corticosterone or metyrapone (an inhibitor of corticosterone synthesis) administration. Sleep parameters were continuously recorded throughout the sleep deprivation period and during 3 days of sleep recovery. Plasma levels of adrenocorticotropic hormone and corticosterone were also evaluated. Metyrapone treatment prevented the elevation of corticosterone plasma levels induced by REM sleep deprivation, whereas corticosterone administration to REM sleep-deprived rats resulted in lower corticosterone levels than in non-sleep deprived rats. Nonetheless, both corticosterone and metyrapone administration led to several alterations on sleep homeostasis, including reductions in the amount of non-REM and REM sleep during the recovery period, although corticosterone increased delta activity (1.0-4.0 Hz) during REM sleep deprivation. Metyrapone treatment of REM sleep-deprived rats reduced the number of REM sleep episodes. in conclusion, reduction of corticosterone levels during REM sleep deprivation resulted in impairment of sleep rebound, suggesting that physiological elevation of corticosterone levels resulting from REM sleep deprivation is necessary for plentiful recovery of sleep after this stressful event.Associacao Fundo de Incentivo a Pesquisa (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 Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilFAPESP: 98/14303-3FAPESP: 04/02213-2Web of Scienc

Role of Corticosterone on Sleep Homeostasis Induced by REM Sleep Deprivation in Rats

Sleep is regulated by humoral and homeostatic processes. If on one hand chronic elevation of stress hormones impair sleep, on the other hand, rapid eye movement (REM) sleep deprivation induces elevation of glucocorticoids and time of REM sleep during the recovery period. in the present study we sought to examine whether manipulations of corticosterone levels during REM sleep deprivation would alter the subsequent sleep rebound. Adult male Wistar rats were fit with electrodes for sleep monitoring and submitted to four days of REM sleep deprivation under repeated corticosterone or metyrapone (an inhibitor of corticosterone synthesis) administration. Sleep parameters were continuously recorded throughout the sleep deprivation period and during 3 days of sleep recovery. Plasma levels of adrenocorticotropic hormone and corticosterone were also evaluated. Metyrapone treatment prevented the elevation of corticosterone plasma levels induced by REM sleep deprivation, whereas corticosterone administration to REM sleep-deprived rats resulted in lower corticosterone levels than in non-sleep deprived rats. Nonetheless, both corticosterone and metyrapone administration led to several alterations on sleep homeostasis, including reductions in the amount of non-REM and REM sleep during the recovery period, although corticosterone increased delta activity (1.0-4.0 Hz) during REM sleep deprivation. Metyrapone treatment of REM sleep-deprived rats reduced the number of REM sleep episodes. in conclusion, reduction of corticosterone levels during REM sleep deprivation resulted in impairment of sleep rebound, suggesting that physiological elevation of corticosterone levels resulting from REM sleep deprivation is necessary for plentiful recovery of sleep after this stressful event.Associacao Fundo de Incentivo a Pesquisa (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 Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilFAPESP: 98/14303-3FAPESP: 04/02213-2Web of Scienc

Immune outcomes of sleep disorders: the hypothalamic-pituitary-adrenal axis as a modulatory factor

OBJECTIVE: To review the literature on the interaction between sleep and the immune system. METHOD: A search on Web of Science and Pubmed database including the keywords sleep, sleep deprivation, stress, hypothalamic-pituitary-adrenal axis, immune system, and autoimmune diseases. RESULTS: On Web of Science, 588 publications were retrieved; 61 references, more significant and closer to our objective, were used, including original articles and review papers. CONCLUSION: Sleep deprivation and immune system exert a bidirectional influence on each other. Since sleep deprivation is considered a stressor, inasmuch as it induces elevation of cortisol or corticosterone levels in humans and rodents, respectively, and given the well-known immunosuppressive effect of glucocorticoids, we propose that increased activation of the hypothalamic-pituitary-adrenal axis is a major mediator of the immune alterations observed in patients with insomnia or in sleep deprived subjects.OBJETIVO: Revisar a literatura a respeito da interação entre sono e sistema imunológico. MÉTODO: Busca no Web of Science e no PubMed com os descritores: sono, privação de sono, estresse, eixo hipotálamo-pituitária-adrenal, sistema imunológico e doenças auto-imunes. RESULTADOS: Foram encontrados 588 artigos no Web of Science. As 61 referências mais significativas e mais relacionadas aos objetivos do estudo foram utilizadas. Foram incluídos artigos originais e de revisão. CONCLUSÃO: A privação de sono e o sistema imunológico exercem e sofrem influências mútuas. A privação de sono é considerada um estressor, uma vez que induz a elevação do cortisol em seres humanos - ou da corticosterona em roedores. Os glicocorticóides, por sua vez, exercem um efeito imunossupressor. Por essas razões, foi proposto que o aumento da ativação do eixo hipotálamo-pituitária-adrenal seja um importante mediador das alterações imunológicas observadas em pacientes com insônia ou privados de sono.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUNIFESP, Depto. de PsicobiologiaSciEL

Pieni sankari

Suomentanut Ivar Elis Sundelin.Joulun aikana. Pieni sankari. Höyrylaivankapteeni ja sotamies. Kaksi lasta, Frans ja Maria