Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats

Kornél Demeter, Bibiána Török, Anna Fodor, János Varga, Szilamér Ferenczi, K. Kovács, Ildikó Eszik, Viktor Szegedi, D. Zelena

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)123-134
Number of pages12
JournalBehavioural Brain Research
Volume300
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

Brattleboro Rats
Vasopressins
Epigenomics
Schizophrenia
Acetylation
Hippocampus
Telemetry
Messenger RNA
Brain-Derived Neurotrophic Factor
Locomotion
Prefrontal Cortex
Cognition
Cell Count
Western Blotting
Immunohistochemistry

Keywords

  • Brattleboro
  • Epigenetics
  • Schizophrenia
  • Vasopressin

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats. / Demeter, Kornél; Török, Bibiána; Fodor, Anna; Varga, János; Ferenczi, Szilamér; Kovács, K.; Eszik, Ildikó; Szegedi, Viktor; Zelena, D.

In: Behavioural Brain Research, Vol. 300, 01.03.2016, p. 123-134.

Research output: Contribution to journalArticle

Demeter, Kornél ; Török, Bibiána ; Fodor, Anna ; Varga, János ; Ferenczi, Szilamér ; Kovács, K. ; Eszik, Ildikó ; Szegedi, Viktor ; Zelena, D. / Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats. In: Behavioural Brain Research. 2016 ; Vol. 300. pp. 123-134.
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