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Epigenetic modulation of glial cells by tobacco smoke after an inflammatory challenge

Grant number: 16/17161-5
Support type:Regular Research Grants
Duration: June 01, 2017 - May 31, 2019
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Tania Marcourakis
Grantee:Tania Marcourakis
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Epigenetic are modifications that occur in that are DNA capable of controlling thetranscriptional process. During the egg's implantation phase, DNA is more vulnerable toexternal influences such as cigarette smoke, increasing the risk of retardation of fetaldevelopment, risk of postnatal sudden death and abnormalities of the immune system.Moreover, children of mothers who smoke develop asthma early justified by changes inF2RL3 and AHRR genes, as well as suppression of transcription factor T-bet, increasedTH2 response and higher performance of chromosome 5q 'TH2'. In this context, the aimof this project is to evaluate the influence of cigarette smoke in the formation of theimmune system of the central nervous system and its consequences in the course of aninflammatory response. For this, C57BL/6 pregnant females mice are exposed to cigarettesmoke from the vaginal plug until the birth of offspring. On the first three days of life,the newborns will be separated to two lines of work: 1) in vivo: the animals will bechallenged with LPS i.p. at a dose of 1 mg kg. After 4 hours, the mice will be euthanizedand CNS removed for analyzes of PCR Array, CBA, flow cytometry and global DNAmethylation. 2) in vitro: the CNS of the newborns will be dissected and used for thepreparation of a mixed glia culture. After 14 days, the cells will be stimulated with LPS100 ng/ml and after 24 hours, the assays CBA, Western blot, flow cytometry and specificgene methylation will be performed. (AU)