Estudo do sistema nociceptivo de camundongos submetidos à redução do tempo de sono durante o período neonatal
Arquivos
Data
2014
Autores
Araujo, Paula Cristina Alves 
Orientadores
Andersen, Monica Levy
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A atividade neural presente durante o sono e um evento fisiologico capaz de promover estimulos endogenos para os sistemas sensoriais que dependem de atividade neural para o desenvolvimento, como o sistema nociceptivo. A reducao do tempo de sono em uma fase critica para a maturacao deste sistema pode resultar em consequencias negativas no desenvolvimento da nocicepcao. Diante disso, o objetivo do presente estudo foi investigar os efeitos da reducao do tempo de sono durante o periodo neonatal no sistema nociceptivo. Ainda, foi avaliado se a reducao do tempo de sono poderia alterar a atividade neural da via nociceptiva. Para isto, na primeira etapa do estudo camundongos com 12 dias de vida (P12) foram distribuidos em tres grupos: controle (CTRL), privacao de sono (PS) e separacao materna (SM). Foi realizada apenas uma unica sessao de PS e SM com duracao de seis horas. Os animais foram avaliados quanto a resposta nociceptiva e comportamento tipo ansioso com 35 e 90 dias de vida. Na segunda etapa, camundongos no P12 foram distribuidos aleatoriamente nos grupos: CTRL, restricao de sono (RS) e SM. A RS e SM foram realizadas durante dez dias (P12 ao P21) duas horas por dia. Os animais foram avaliados quanto a resposta comportamental nociceptiva logo apos a manipulacao (P21), na adolescencia (P35) e vida adulta (P90). Nesta etapa tambem avaliamos se as alteracoes na nocicepcao estariam relacionadas com mudancas na atividade neural da via nociceptiva. Os resultados demonstraram que a tanto a PS quanto a RS foram capazes de aumentar a sensibilidade nociceptiva nos animais adolescentes. Entretanto, esta mudanca na resposta nociceptiva induzida pela perda de sono cronica nao foi acompanhada por alteracoes na expressao da proteina c-Fos, um marcador de atividade neural, no cortex cingulado anterior e cortex somatosensorial. O comportamento pronociceptivo presente na adolescencia nao persistiu ate a vida adulta. Em conjunto, os achados deste estudo indicam que a reducao do tempo de sono em um periodo critico para a maturacao da resposta nociceptiva induz aumento da sensibilidade em camundongos adolescentes, refletindo um possivel papel do sono no desenvolvimento do sistema nociceptivo
Sleep in neonates is a physiological event able to promote proper brain activity to the sensory systems in which development is dependent upon activity. Sleep loss can lead to negative implications for the maturation process of nociceptive system. We tested the hypothesis that neonatal sleep reduction induces a long-term increase on nociceptive response in mice, and that this hypersensitivity occurs by means of changes in the activity of nociceptive pathways. In the fist phase, neonatal mice at postnatal day (PND) 12 were randomly assigned to the following groups: control group (CTRL), sleep deprivation (SD) and maternal separation (MS). The method of gentle handling was used to prevent sleep. All the manipulations were performed during six hours. At PND 22, mice were group housed by litter and sex. At PND 35 and PND 90, they were tested for nociceptive and anxiety behaviors. In the second phase, mice at PND 12 were randomly assigned to the following groups: CTRL, sleep restriction (SR) and MS. The SR and MS were performed two hours by day during ten days (PND 12 until PND 21). For each developmental time-point (PND 21, 35 and 90), mice were tested for pain-related behaviors. The results showed that in juvenile mice the nociceptive thermal threshold was significantly lower in SD mice compared to CTRL animals. In the same line, the SR increased the nociceptive sensitivity in adolescent mice submitted to the hot plate test. However, this alteration in nociceptive response was not followed by changes in c-Fos expression, a neuronal activity marker, in the anterior cingulate cortex and primary somatosensory cortex. In both protocols, the changes in pain sensitivity did not persist until adulthood with all mice showed comparable nociceptive response. The current findings indicate that exposure to sleep loss during early-life period are able to induce mild-term changes in nociceptive response.
Sleep in neonates is a physiological event able to promote proper brain activity to the sensory systems in which development is dependent upon activity. Sleep loss can lead to negative implications for the maturation process of nociceptive system. We tested the hypothesis that neonatal sleep reduction induces a long-term increase on nociceptive response in mice, and that this hypersensitivity occurs by means of changes in the activity of nociceptive pathways. In the fist phase, neonatal mice at postnatal day (PND) 12 were randomly assigned to the following groups: control group (CTRL), sleep deprivation (SD) and maternal separation (MS). The method of gentle handling was used to prevent sleep. All the manipulations were performed during six hours. At PND 22, mice were group housed by litter and sex. At PND 35 and PND 90, they were tested for nociceptive and anxiety behaviors. In the second phase, mice at PND 12 were randomly assigned to the following groups: CTRL, sleep restriction (SR) and MS. The SR and MS were performed two hours by day during ten days (PND 12 until PND 21). For each developmental time-point (PND 21, 35 and 90), mice were tested for pain-related behaviors. The results showed that in juvenile mice the nociceptive thermal threshold was significantly lower in SD mice compared to CTRL animals. In the same line, the SR increased the nociceptive sensitivity in adolescent mice submitted to the hot plate test. However, this alteration in nociceptive response was not followed by changes in c-Fos expression, a neuronal activity marker, in the anterior cingulate cortex and primary somatosensory cortex. In both protocols, the changes in pain sensitivity did not persist until adulthood with all mice showed comparable nociceptive response. The current findings indicate that exposure to sleep loss during early-life period are able to induce mild-term changes in nociceptive response.
Descrição
Citação
ARAUJO, Paula Cristina Alves. Estudo do sistema nociceptivo de camundongos submetidos à redução do tempo de sono durante o período neonatal. 2014. 142 f. Tese (Doutorado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2014.