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

Pre-test metyrapone impairs memory recall in fear conditioning tasks: lack of interaction with I--adrenergic activity

Cognitive processes, such as learning and memory, are essential for our adaptation to environmental changes and consequently for survival. Numerous studies indicate that hormones secreted during stressful situations, such as glucocorticoids (GCs), adrenaline and noradrenaline, regulate memory functions, modulating aversive memory consolidation and retrieval, in an interactive and complementary way. Thus, the facilitatory effects of GCs on memory consolidation as well as their suppressive effects on retrieval are substantially explained by this interaction. On the other hand, low levels of GCs are also associated with negative effects on memory consolidation and retrieval and the mechanisms involved are not well understood. the present study sought to investigate the consequences of blocking the rise of GCs on fear memory retrieval in multiple tests, assessing the participation of (3-adrenergic signaling on this effect. Metyrapone (GCs synthesis inhibitor; 75 mg/kg), administered 90 min before the first test of contextual or tone fear conditioning (TFC), negatively affected animals' performances, but this effect did not persist on a subsequent test, when the conditioned response was again expressed. This result suggested that the treatment impaired fear memory retrieval during the first evaluation. the administration immediately after the first test did not affect the animals' performances in contextual fear conditioning (CFC), suggesting that the drug did not interfere with processes triggered by memory reactivation. Moreover, metyrapone effects were independent of beta-adrenergic signaling, since concurrent administration with propranolol (2 mg/kg), alpha,beta-adrenergic antagonist, did not modify the effects induced by metyrapone alone. These results demonstrate that pre-test metyrapone administration led to negative effects on fear memory retrieval and this action was independent of a beta-adrenergic signaling.Associacao Fund de Incentivo a Pesquisa (AFIP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao de Amparo Pesquisa do Estado de São PauloUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniv Fed ABC, Ctr Matemat Comp & Cognicao, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilFundacao de Amparo Pesquisa do Estado de São Paulo: FAPESP 2011/16977-8Web 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

Effects of sleep deprivation on different phases of memory in the rat: dissociation between contextual and tone fear conditioning tasks

Numerous studies show that sleep deprivation (SD) impacts negatively on cognitive processes, including learning and memory. Memory formation encompasses distinct phases of which acquisition, consolidation and retrieval are better known. Previous studies with pre-training SD induced by the platform method have shown impairment in fear conditioning tasks. Nonetheless, pre-training manipulations do not allow the distinction between effects on acquisition and/or consolidation, interfering, ultimately, on recall of/performance in the task. in the present study, animals were first trained in contextual and tone fear conditioning (TFC) tasks and then submitted to SD with the purpose to evaluate the effect of this manipulation on different stages of the learning process, e.g., in the uptake of (new) information during learning, its encoding and stabilization, and the recall of stored memories. Besides, we also investigated the effect of SD in the extinction of fear memory and a possible state dependent learning induced by this manipulation. for each task (contextual or TFC), animals were trained and then distributed into control, not sleep-deprived (CTL) and SD groups, the latter being submitted to the modified multiple platform paradigm for 96 h. Subsets of eight rats in each group/experiment were submitted to the test of the tasks, either immediately or at different time intervals after SD. the results indicated that (a) pre- but not post-training SD impaired recall in the contextual and TFC; (b) this impairment was not state-dependent; and (c) in the contextual fear conditioning (CFC), pre-test SD prevented extinction of the learned task. Overall, these results suggest that SD interferes with acquisition, recall and extinction, but not necessarily with consolidation of emotional memory.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo UNIFESP, Dept Psychobiol, Escola Paulista Med, BR-04024002 São Paulo, BrazilUniv Fed ABC UFABC, Ctr Matemat, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psychobiol, Escola Paulista Med, BR-04024002 São Paulo, BrazilFAPESP: 2012/23488-6Web of Scienc

Effects of early handling and maternal separation on baseline and cold stress-induced sleep pattern in adult rats

Eventos adversos na infancia resultam em alteracao da resposta do eixo hipotalamohipofise-adrenal ao estresse. O impacto de niveis elevados de ACTH e corticosterona no sono e bem conhecidos. O presente estudo procurou avaliar o padrao de sono basal e apos o estresse de frio em animais submetidos a estimulacao neonatal (15 mm/dia separados da mae) e a separacao materna (180 min/dia distantes da mae), comparados aos animais controle nao manipulados. As manipulacoes foram realizadas entre os dias 2 e 14 de vida, e o padrao de sono foi avaliado nos animais machos adultos. Apos a recuperacao da cirurgia de implante de eletrodos no cortex cerebral e no musculo do pescoco, o sono basal dos animais foi registrado durante 22h (tendo inicio as 09:00 h). No dia seguinte, os ratos foram expostos ao estresse de frio (lh a 4°C) e o sono foi novamente registrado por outras 22h. Animais separados da mae apresentaram mais sono paradoxal na situacao basal, em comparacao com os grupos estimulacao neonatal e controle. Em resposta ao estresse de frio, todos os grupos apresentaram uma resposta hormonal semelhante, com picos de concentracao plasmatica imediatamente apos o termino da exposicao ao estressor. Da mesma forma, todos os grupos apresentaram rebote de sono durante o periodo escuro do ciclo claro-escuro. Estes resultados indicam que a separacao materna durante a infancia resulta em uma arquitetura distinta do sono basal, refletida por aumento de tempo despendido em sono paradoxal. As discrepancias entre os resultados encontrados neste trabalho e os descritos na literatura quanto a atividade do eixo hipotalamo-hipofise-adrenal sao discutidas em termos do impacto destas manipulacoes no comportamento materno voltado para os filhotes e das diferentes linhagens de ratosBV UNIFESP: Teses e dissertaçõe

Pre-test metyrapone impairs memory recall in fear conditioning tasks: lack of interaction with beta-adrenergic activity (vol 9, pg 51, 2015)

Universidade Federal de São Paulo, Dept Psicobiol, Escola Paulista Med Neurobiol Stress & Stress Rel, São Paulo, BrazilUniv Fed ABC, Ctr Matemat Comp & Cognicao, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, Escola Paulista Med Neurobiol Stress & Stress Rel, São Paulo, BrazilWeb of Scienc