A novel genetic animal model for bipolar disorder

M Jukic, A Avin, T Baron, M Bar, K Zega, O Novikov, A Tarasiuk, O Kofman, C Brodski

Research output: Contribution to journalMeeting Abstract

Abstract

Genetic predisposition and dysfunction of monoaminergic
neurons are thought to play a critical role in bipolar disorder.
However, how these factors interact in the pathophysiology
and pharmacotherapy of this disease is poorly understood.
Previously, we demonstrated that the embryonic midhindbrain organizer, which is composed of a transient cell
population in the brainstem, controls the development of
dopaminergic and serotonergic neurons. Recently, midhindbrain organizer
associated genes have been suggested as susceptibility
genes for bipolar disorder. The aim of the present study
was to test the face and predictive validity of midhindbrain organizer mouse mutants as a model for bipolar
disorder. To this
end we investigated manic- and depressive-like behaviour in
these mutants and studied whether these behaviours can be
reversed by mood stabilizing drugs. In addition, neuropathological changes that have been associated with bipolar
disorder were studied in these mice, providing insights into
the molecular basis of the altered behaviour of the mutants.
We found that mutants are hyperactive and showed increased risk taking behavior. Importantly, mutants showed
in contrast to wild-types intra-individual fluctuations in their
locomotor activity, hedonic and risk taking behavior. In
addition, mutants showed an increase in risk taking behaviour.
Olanzapine and lithium, which are used for the treatment of
mania, reversed some of behavioural alterations in mutants.
The establishment of mid-hindbrain
organizer mutants as a model for bipolar disorder will provide a tool to investigate particular aspects of the pathophysiology of this devastating disease and will serve a
rationale towards the development of novel and efficient
mood stabilizing drugs.
Original languageEnglish GB
Pages (from-to)s58-s58
Number of pages1
JournalJournal of Molecular Neuroscience
Volume51
Issue number1
StatePublished - 2013

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