Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression

Ayelet Kaminitz, Ran Barzilay, Hadar Segal, Michal Taler, Daniel Offen, Irit Gil-Ad, Raphael Mechoulam, Abraham Weizman

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1). Methods. DN-DISC1 mice underwent behavioural tests to evaluate object recognition, social preference and social novelty seeking. ELISA was conducted on brain tissue to evaluate BDNF levels. Western blot was employed to measure BDNF receptor (TrkB) and cannabinoid receptor CB1. Results. The mutant DISC1 mice displayed deficits in preference to social novelty while both social preference and object recognition were intact. Biochemical analysis of prefrontal cortex and hippocampus revealed a modest reduction in cortical TrkB protein levels of male mice while no differences in BDNF levels were observed. We found sex dependent differences in the expression of cannabinoid-1 receptors. Conclusions. We describe novel behavioural and biochemical abnormalities in the DN-DISC1 mouse model of schizophrenia. The data shows for the first time a possible link between DISC1 mutation and the cannabinoid system.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalWorld Journal of Biological Psychiatry
Volume15
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Animal model
  • BDNF
  • CB1
  • DISC1
  • Schizophrenia

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