Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test.

Autor: de Esch CE; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., van den Berg WE; Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands., Buijsen RA; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., Jaafar IA; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., Nieuwenhuizen-Bakker IM; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., Gasparini F; Novartis Institutes for BioMedical Research Basel, Switzerland., Kushner SA; Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands., Willemsen R; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands. Electronic address: r.willemsen@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2015 Mar; Vol. 75, pp. 31-9. Date of Electronic Publication: 2015 Jan 03.
DOI: 10.1016/j.nbd.2014.12.021
Abstrakt: Fragile X syndrome is the most common monogenetic form of intellectual disability and autism. Although the Fmr1 knockout mouse model recapitulates many aspects of the human FXS condition, the establishment of robust social behavioural phenotypes suitable for drug screening has been difficult. Here, we describe a novel social behavioural paradigm, the Automated Tube Test (ATT), for which Fmr1 knockout mice demonstrate a highly reliable and robust phenotype. Fmr1 KO mice show highly dominant behaviour over wild-type littermates in the ATT. Consistent with previous findings, we observed a highly significant, albeit partial, rescue of the altered social behaviour of Fmr1 knockout mice in the ATT, using genetic (mGluR5 deletion) or pharmacological inhibition (mGluR5 antagonist) of mGluR5 signalling independently. Together, our results validate the Automated Tube Test as a robust outcome measure for social behaviour in preclinical research for FXS, and confirm the pathophysiological relevance of mGluR5 signalling. Moreover, our findings highlight the strategy of initiating pharmacological intervention in adulthood as holding significant clinical potential.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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