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Study of epigenetic alterations in GABAergic neurotransmission in schizophrenia and other psychoses and in animals undergoing social isolation from weaning

Grant number: 15/02948-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2015
Effective date (End): May 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Cristina Marta Del-Ben
Grantee:Helene Aparecida Fachim
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:12/05178-0 - Schizophrenia and other psychotic disorders: social and biological determinants, AP.TEM
Associated scholarship(s):17/00624-5 - DNA methylation investigation in first episode of psychosis and in rats undergoing isolation rearing from weaning in the two major excitatory and inhibitory systems, BE.EP.PD

Abstract

A large body of evidence suggests that schizophrenia is a disease which occurs during the development of central nervous system (CNS) which results from the combination of both genetic and environmental factors. Several studies have shown that GABAergic neurotransmission is affected in this disease, among these abnormalities there is a decrease in reelin, parvalbumin and GAD67 levels. These changes have been found in both postmortem human brain and in animal models of the disease. Despite the significant efforts of several areas of research, little progress has been made in understanding the genetic and environmental basis of schizophrenia. Thus epigenetic mechanisms seem to be excellent targets to the study of the aetiology of psychosis. Furthermore, the translational study will allow improved workability of new treatment strategies. Despite this evidence, little is known about the levels of methylation of promoter regions of gene encoding these proteins both in the disease and in the animal models also the reduction in the expression thereof occurs due to hypermethylation of the promoter region of these genes. The aim of this study is to evaluate the occurrence of hypermethylation in the promoter regions of the genes which encode the proteins reelin, parvalbumin and GAD67, in both peripheral blood samples of patients after the first psychotic episode, and in blood samples and also brain tissue of animals undergoing social isolation from weaning.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FACHIM, HELENE A.; LOUREIRO, CAMILA M.; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; LOUZADA, JR., PAULO; MENEZES, PAULO ROSSI; DALTON, CAROLINE F.; DEL-BEN, CRISTINA MARTA; REYNOLDS, GAVIN P. GRIN2B promoter methylation deficits in early-onset schizophrenia and its association with cognitive function. Epigenomics, v. 11, n. 4, p. 401-410, MAR 2019. Web of Science Citations: 0.
CORSI-ZUELLI, FABIANA; FACHIM, HELENE APARECIDA; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; BERTOZI, GIULIANO; JOCA, SAMIA REGIANE LOURENGO; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain. FRONTIERS IN NEUROSCIENCE, v. 12, JAN 11 2019. Web of Science Citations: 0.
FACHIM, HELENE A.; SRISAWAT, UMARAT; DALTON, CAROLINE F.; HARTE, MICHAEL K.; MARSH, SAMUEL; NEILL, JOANNA C.; REYNOLDS, GAVIN P. Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain. Epigenomics, v. 8, n. 9, p. 1179-1183, SEP 2016. Web of Science Citations: 8.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.