relation: http://publicatio.bibl.u-szeged.hu/12347/
title: Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats
creator:  Demeter Kornél
creator:  Török Bibiána
creator:  Fodor Anna
creator:  Varga János
creator:  Ferenczi Szilamér
creator:  Kovács Krisztina J
creator:  Eszik Ildikó
creator:  Szegedi Viktor
creator:  Zelena Dóra
description: Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR. Histone3 (H3) and H4 acetylation (Ac) were studied by western-blot followed by region specific examination of H3 lysine9 (K9) acetylation by immunohistochemistry. Impaired cognitive, social and attention behavior of di/di rats confirmed schizophrenia-like symptoms in our local colony. The pan-AcH3 immunoreactivity was lower in prefrontal region and elevated in the hippocampus of di/di animals. We found lower immunopositive cell number in the dorsal peduncular prefrontal cortex and the ventral lateral septum and increased AcH3K9 immunoreactivity in CA1 region of di/di animals. There were no major significant alterations in the studied mRNA levels. We confirmed that Brattleboro rat is a good preclinical model of schizophrenia. Its schizophrenia-like behavioral alteration was accompanied by changes in H3 acetylation in the prefrontal region and hippocampus. This may contribute to disturbances of many schizophrenia-related substances leading to development of schizophrenia-like symptoms. Our studies confirmed that not a single gene, rather fine changes in an array of molecules are responsible for the majority of schizophrenia cases.
date: 2016-03-01
type: Folyóiratcikk
type: NonPeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/12347/1/1-s2.0-S016643281530317X-main.pdf
identifier:     Demeter Kornél;  Török Bibiána;  Fodor Anna;  Varga János;  Ferenczi Szilamér;  Kovács Krisztina J;  Eszik Ildikó;  Szegedi Viktor;  Zelena Dóra: Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats.   Behavioural brain research, 300.  pp. 123-134.  ISSN 1872-7549 (2016)     
identifier: doi:10.1016/j.bbr.2015.12.007
relation: 2987113
language: eng
relation: info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbr.2015.12.007
rights: info:eu-repo/semantics/openAccess