Publicação
Impact of dexamethasone in the enteric nervous system
| Resumo: | Synthetic glucocorticoids are routinely administered to pregnant women at risk of premature labor. The effect of this administration has been studied both in humans and in rodents, since antenatal exposure to dexamethasone (DEX) causes persistent alterations in the central nervous system (CNS). Despite the greatly improved survival of preterm babies with prenatal DEX administration, little is known about possible adverse effects of this treatment in the enteric nervous system (ENS). The animal model used in this study - in utero exposure to synthetic glucocorticoids (iuGC) - consists in the administration of DEX (1 mg/kg) in the 18 and 19 days of gestation of pregnant female Wistar rats. Stomach, small and large intestine, of the male offspring, for both iuGC and control (CTR) groups, were evaluated morphometrically. As iuGC rats showed a shorter small intestine, in vivo functional tests were done in the upper gastrointestinal (GI) intestine (transit and permeability). It was shown that iuGC rats have a slow transit, despite normal permeability. Serotonin (5-HT) levels and cellular turnover rate were measured at different ages (1, 3 and 8 months old). iuGC rats at 3 months old have a decrease in 5-HT content, while proliferation and apoptosis rates were altered in all ages. Then, using a video recording and spatiotemporal map construction, we study ex vivo jejunum and colonic contractions, which confirmed that iuGC rats have a decrease of migrating motor complex (MMC) in jejunum at 1 month old and decreased of colonic MMC at 3 months old. Furthermore, we found a unique jejunum pattern motility in the first 5 centimetres, whose rhythmicity of the contractions sets (intercalated by quiescent periods) were identical in both groups. To further investigate these effects, particular subpopulations of myenteric neurons were analysed. We used immunohistochemistry to count numbers of neurons (expressing Hu), numbers of neurons expressing neuronal nitric oxide synthase (nNOS) and numbers of neurons expressing calbindin or calretinin. The number of calretinin (presumably cholinergic) neurons were altered in jejunum and colon of iuGC rats, while calbindin and nNOS neurons are unchanged. These data indicate that intrauterine administration of DEX impacts morphometric and functionally the GI tract. Additionally, the ex vivo motility assays suggest that the changes induced by iuGC in motility are partly independent of CNS input. |
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| Autores principais: | Ramalhosa, Fátima Marques |
| Assunto: | Ciências Médicas::Ciências da Saúde |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Synthetic glucocorticoids are routinely administered to pregnant women at risk of premature labor. The effect of this administration has been studied both in humans and in rodents, since antenatal exposure to dexamethasone (DEX) causes persistent alterations in the central nervous system (CNS). Despite the greatly improved survival of preterm babies with prenatal DEX administration, little is known about possible adverse effects of this treatment in the enteric nervous system (ENS). The animal model used in this study - in utero exposure to synthetic glucocorticoids (iuGC) - consists in the administration of DEX (1 mg/kg) in the 18 and 19 days of gestation of pregnant female Wistar rats. Stomach, small and large intestine, of the male offspring, for both iuGC and control (CTR) groups, were evaluated morphometrically. As iuGC rats showed a shorter small intestine, in vivo functional tests were done in the upper gastrointestinal (GI) intestine (transit and permeability). It was shown that iuGC rats have a slow transit, despite normal permeability. Serotonin (5-HT) levels and cellular turnover rate were measured at different ages (1, 3 and 8 months old). iuGC rats at 3 months old have a decrease in 5-HT content, while proliferation and apoptosis rates were altered in all ages. Then, using a video recording and spatiotemporal map construction, we study ex vivo jejunum and colonic contractions, which confirmed that iuGC rats have a decrease of migrating motor complex (MMC) in jejunum at 1 month old and decreased of colonic MMC at 3 months old. Furthermore, we found a unique jejunum pattern motility in the first 5 centimetres, whose rhythmicity of the contractions sets (intercalated by quiescent periods) were identical in both groups. To further investigate these effects, particular subpopulations of myenteric neurons were analysed. We used immunohistochemistry to count numbers of neurons (expressing Hu), numbers of neurons expressing neuronal nitric oxide synthase (nNOS) and numbers of neurons expressing calbindin or calretinin. The number of calretinin (presumably cholinergic) neurons were altered in jejunum and colon of iuGC rats, while calbindin and nNOS neurons are unchanged. These data indicate that intrauterine administration of DEX impacts morphometric and functionally the GI tract. Additionally, the ex vivo motility assays suggest that the changes induced by iuGC in motility are partly independent of CNS input. |
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