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ZULIAN, J . G . Cell differentiation in the gastric epithelium of early weaned rats: corticosterone action evaluation. 2016. 84 p. Ph.D Thesis (Cell and Tissue Biology) Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 2016. The epithelium of the stomach corpus is lined by long tubular glands. The foveolas are covered by surface mucous cells and in the glands we have parietal cells, mucous neck cell and zymogenic cells. The rat ́s gastric mucosa completes the maturation process during the third post-natal week, throughout the food transition process. At 14 th day, the pups begin to eat chow with maternal milk and at 21 st day the weaning, for experimental animals, is complete. The early weaning consists in the abrupt suckling interruption at 15 th day. This diet modification is related to accelerated maturation process of diverse organs, increase in mucous neck cells differentiation and in corticosterone levels (the main glucocorticoid hormone in rats). The glucocorticoids (GCs) action can be inhibited by RU486, a glucocorticoid receptor antagonist. The aim of this study was to evaluate if the increase in corticosterone levels triggered to early weaning could affect gastric epithelium maturation and to verify if these changes could persist to adult age. For that, we had four experimental groups: suckling, suckling-RU486, early weaning and early weaning-RU486. Using RT-qPCR, in 17-d-old rats, we observed that early weaning increased Muc5ac, Bhlha15 and Pgc and decreased Msn (comparing suckling-RU486 and early weaning-RU486) and Pga5 expression, while RU486 reverted the results for Pgc and Muc5ac, reduced Gif expression in early weaning-RU486, reduced Fut1 expresion in suckling-RU486 and increased Muc6 expression (genes related to gastric maturation process). The efficiency of RU486 treatment was attested by the reduction of SGK1 mRNA levels, which were elevated by early weaning. Mucous neck cells population was evaluated using the histochemistry reactions of PASAB and GSII lectin, and the immune-hystochemistry for mucin 6. In 17 and 18-d-old animals, we noted that early weaning increased mucous neck cells number as RU486 reverted this result. The zymogenic cells were analysed with immune-histochemistry reactions for Mist1 and for pepsinogen C (PGC). In pups, we found that early weaning increased Mist1-positive and PGC-positive cells populations, although corticosterone inhibition reverted only the result for PGC. In 30-d-old rats, we had the following results: reduction on Fut1 expression caused by early weaning; reduction on mRNA levels for moesin in SRU and early weaning groups, and elevation on early weaning-RU486; reduction on Pga5 expression provoked by RU486; the results over Pgc were maintained; the results, caused both by early weaning as RU486, over the population of mucous neck cells positives for PASAB and positives for mucin 6 were maintained, as well as the effects of RU486 over PGC immune-stained cells. We concluded that the increase in corticosterone levels, caused by early weaning, has a fundamental role in the mucous neck cells and zymogenic cells complete differentiation.

Diferenciação celular no epitélio gástrico de ratos submetidos ao desmame precoce: avaliação da ação da corticosterona.