Restrição crônica de sono REM durante o período juvenil altera comportamentos hedônico e tipo-ansioso de forma dependente do sexo em ratos Wistar adolescentes
Data
2022-10-07
Autores
Barreto, Anna Carolina Muniz 
Orientadores
Suchecki, Deborah
Tipo
Dissertação de mestrado
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ISSN da Revista
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Resumo
Restrição crônica de sono REM durante o período juvenil altera comportamentos hedônico e tipo-ansioso de forma dependente do sexo em ratos Wistar adolescentes.
Introdução: A restrição crônica de sono REM (acrônimo de rapid eye movements) é considerada um estressor. Em seres humanos, a redução prolongada do tempo de sono na adolescência tem sido relacionada ao aumento de ansiedade e depressão. Objetivos: Avaliar os efeitos da restrição crônica de sono REM (RSREM) em ratos Wistar adolescentes, machos e fêmeas, sobre comportamentos emocionais e parâmetros hormonais. Métodos: 22 Ninhadas foram obtidas no biotério do Departamento de Psicobiologia e padronizadas para 4 machos e 4 fêmeas no dia pós natal (DPN) 1. Os animais foram alojados com irmãos/irmãs, em grupos de 4 animais. A restrição de sono foi realizada pelo método modificado das plataformas múltiplas, por 21 dias, a partir do DPN 21 até o DPN 42. Neste protocolo, os animais eram colocados no ambiente de privação de sono por 18 h (entre 16:00 h e 10:00 do dia seguinte) e alojados em suas gaiolas por 6 h. Para a avaliação comportamental foi utilizado o teste de splash de sacarose (TSS) ao longo do protocolo de RSREM. Após o fim do protocolo de RSREM os animais do grupo RSREM puderam dormir livremente por um período de 48 h. Após esse período 1/4 dos animais, em cada sexo, não foi submetida a testes comportamentais (não testados: NT), 1/4 foi submetido ao teste de contraste positivo de sacarose (TCPS), 1/4 ao labirinto em cruz elevado (LCE) e o último 1/4, ao teste do nado forçado (TNF). Todos os animais foram pesados nos DPNs 21 e 42, para mensuração de ganho de peso corporal. Os animais foram submetidos a eutanásia, pelo método de decapitação, trinta minutos após o término dos testes comportamentais ou no tempo correspondente para os animais NT. Foi realizada a determinação do peso relativo as glândulas adrenais no dia da eutanásia. O dia da fase do ciclo estral no qual as ratas encontravam-se no dia da eutanásia foi determinado por esfregaço vaginal. Além disso foram determinadas as concentrações plasmáticas de estrogênio (EST) nas fêmeas submetidas ao LCE e TNF, de testosterona (TESTO) nos machos submetidos ao LCE e TNF, de corticosterona (CORT) em todos os animais e de Fator Neurotrófico Derivado do Cérebro (BDNF) no hipocampo dorsal dos animais NT. Resultados: A RSREM reduziu a frequência de autolimpeza no TSS e o ganho de peso corporal em ambos os sexos. Em comparação aos grupos CTL, as fêmeas RSREM apresentaram redução da imobilidade no TNF. No LCE, apenas os machos do grupo RSREM apresentaram aumento de comportamentos relevantes para o estudo da ansiedade e no TCPS não foram observadas diferenças entre os grupos em ambos os sexos. As fêmeas RSREM liberaram menores concentrações de CORT do que as fêmeas CTL em todas as condições experimentais. Entre os machos, não foram observadas diferenças nas concentrações basais ou em resposta aos testes comportamentais entre os grupos CTL e RSREM. Porém, em ambos os grupos, a resposta de CORT ao LCE e TNF foi maior do que os valores basais e pós-TCPS. Além disso os animais submetidos ao TNF apresentaram maiores concentrações de CORT em comparação as demais condições (NT, LCE e TCPS) em ambos os sexos e grupos (CTL e RSREM). Foi observado aumento do peso relativo das adrenais nos machos, mas não nas fêmeas, do grupo RSREM. Não foram observadas diferenças nas concentrações de EST, TESTO e BDNF. Conclusão: Os resultados indicam que a RSREM prejudicou o comportamento de auto-cuidado em ambos os sexos. Após o período de recuperação do sono, as fêmeas RSREM não diferiam das fêmeas CTL, enquanto que os machos RSREM apresentavam aumento de comportamentos relevantes para o estudo da ansiedade. Também é possível inferir, a partir dos resultados de CORT, que o TNF correspondeu a condição de teste comportamental, pós recuperação de sono, mais estressante quando comparado aos demais testes utilizados (LCE e TCPS). Os resultados comportamentais observados não foram dependentes do status dos hormônios sexuais, além disso a RSREM por si só não afetou as concentrações de BDNF no hipocampo dorsal.
Chronic REM sleep restriction during the juvenile period alters hedonic and anxiety-like behaviors in a sex-dependent in adolescent Wistar rats. Introduction: Chronic rapid eye movement (REM) sleep restriction (REMSR) is considered a stressor. In humans, prolonged reduction of sleep time in adolescence has been correlated to increased anxiety and depression. Objectives: To analyse the effects REMSR in male and female Wistar rats during adolescence on emotional behaviors and hormonal parameters. Methods: 22 Litters were born in the Department of Psychobiology and on postnatal (PND) 1, were standardized to four males and four females. After weaning, the animals were housed in same-sex littermates, as 4 animals/cage. Sleep restriction was performed by the modified multiple platform method for 21 days, from postnatal day (PND) 21 to PND 42. In this protocol, the animals were sleep deprived for 18 h (between 4:00 pm and 10:00 am of the following day) and allowed to sleep freely in their home-cage for 6 h. During the 21 days of REMSR, all animals were submitted to the sucrose splash test (SST), once a week, beginning immediately before the protocol; the latency to and the frequency of grooming behaviour were recorded. After this period, they were allowed to recover for 48 h. One male and one female in each litter were assigned to one of the following conditions: 1) non-tested (NT), 2) sucrose positive contrast test (SPCT), elevated plus maze (EPM), and 4) forced swimming test (FST). All animals were weighed on PNDs 21 and 42. On the day of euthanasia, the relative weight of the adrenal glands was determined. The animals were euthanized, by the decapitation method, thirty minutes after the end of the behavioral tests or at the corresponding time for NT animals. As well as the phase of the estrous cycle, by vaginal smear. Blood samples were collected for determination of corticosterone, estrogen (EST) in females submitted to EPM and FST and testosterone (TESTO) in males submitted to EPM and FST. Brain-Derived Neurotrophic Factor (BDNF) levels were determined in the dorsal hippocampus of NT animals. Results: REMSR reduced the frequency of grooming in the SST and body weight gain in both sexes. Analysis of the EPM showed that only REMSR males displayed increased anxiety-like behaviorus, whereas in the SPCT no group or sex differences were observed. Compared to CTL groups, REMSR females showed less immobility in the FST. Moreover, REMSR females exhibited lower CORT have increased levels than CTL ones under all testing conditions. For males, we did not find group differences in CORT levels. However, in both sexes, the CORT response to EPM was higher than baseline and post-SPCT values and that to FST was the highest. REMSR induced adrenal hypertrophy in males, but not that observed in females. No group differences were obtained in EST, TESTO, and BDNF concentrations. Conclusion: The results indicate that REMSR impaired self-care behaviour in both sexes. Interestingly, after the sleep recovery period, REMSR females were no longer different from CTL females, whilst REMSR males displayed increased anxiety-like behaviorus. The results also indicated that FST was the most stressful test. The observed behavioural outcomes were not dependent on sex hormones status, and REMRS, by itself did not affect BDNF levels in the dorsal hippocampus.
Chronic REM sleep restriction during the juvenile period alters hedonic and anxiety-like behaviors in a sex-dependent in adolescent Wistar rats. Introduction: Chronic rapid eye movement (REM) sleep restriction (REMSR) is considered a stressor. In humans, prolonged reduction of sleep time in adolescence has been correlated to increased anxiety and depression. Objectives: To analyse the effects REMSR in male and female Wistar rats during adolescence on emotional behaviors and hormonal parameters. Methods: 22 Litters were born in the Department of Psychobiology and on postnatal (PND) 1, were standardized to four males and four females. After weaning, the animals were housed in same-sex littermates, as 4 animals/cage. Sleep restriction was performed by the modified multiple platform method for 21 days, from postnatal day (PND) 21 to PND 42. In this protocol, the animals were sleep deprived for 18 h (between 4:00 pm and 10:00 am of the following day) and allowed to sleep freely in their home-cage for 6 h. During the 21 days of REMSR, all animals were submitted to the sucrose splash test (SST), once a week, beginning immediately before the protocol; the latency to and the frequency of grooming behaviour were recorded. After this period, they were allowed to recover for 48 h. One male and one female in each litter were assigned to one of the following conditions: 1) non-tested (NT), 2) sucrose positive contrast test (SPCT), elevated plus maze (EPM), and 4) forced swimming test (FST). All animals were weighed on PNDs 21 and 42. On the day of euthanasia, the relative weight of the adrenal glands was determined. The animals were euthanized, by the decapitation method, thirty minutes after the end of the behavioral tests or at the corresponding time for NT animals. As well as the phase of the estrous cycle, by vaginal smear. Blood samples were collected for determination of corticosterone, estrogen (EST) in females submitted to EPM and FST and testosterone (TESTO) in males submitted to EPM and FST. Brain-Derived Neurotrophic Factor (BDNF) levels were determined in the dorsal hippocampus of NT animals. Results: REMSR reduced the frequency of grooming in the SST and body weight gain in both sexes. Analysis of the EPM showed that only REMSR males displayed increased anxiety-like behaviorus, whereas in the SPCT no group or sex differences were observed. Compared to CTL groups, REMSR females showed less immobility in the FST. Moreover, REMSR females exhibited lower CORT have increased levels than CTL ones under all testing conditions. For males, we did not find group differences in CORT levels. However, in both sexes, the CORT response to EPM was higher than baseline and post-SPCT values and that to FST was the highest. REMSR induced adrenal hypertrophy in males, but not that observed in females. No group differences were obtained in EST, TESTO, and BDNF concentrations. Conclusion: The results indicate that REMSR impaired self-care behaviour in both sexes. Interestingly, after the sleep recovery period, REMSR females were no longer different from CTL females, whilst REMSR males displayed increased anxiety-like behaviorus. The results also indicated that FST was the most stressful test. The observed behavioural outcomes were not dependent on sex hormones status, and REMRS, by itself did not affect BDNF levels in the dorsal hippocampus.
Descrição
Citação
BARRETO, A C M. Restrição crônica de sono REM durante o período juvenil altera comportamentos hedônico e tipo-ansioso de forma dependente do sexo em ratos Wistar adolescentes. São Paulo, 2022. 65 f. Dissertação (Mestrado em Psicobiologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). São Paulo, 2022.