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Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency.


Cheah, Pike See and Ramshaw, H. S. and Thomas, P. Q. and Toyo-oka, K. and Xu, X. and Martin, S. and Coyle, P. and Guthridge, M. A. and Stomski, F. and Van den Buuse, M. and Wynshaw-Boris, A. and Lopez, A. F. and Schwarz, Q. P. (2012) Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. Molecular Psychiatry, 17 (4). pp. 451-466. ISSN 1359-4184; ESSN: 1476-5578


Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Medicine and Health Science
DOI Number: https://doi.org/10.1038/mp.2011.158
Publisher: Nature Publishing Group
Keywords: Neurodevelopment; Neuropsychiatric disorder; Schizophrenia; Synapse; 14-3-3z.
Depositing User: Nur Farahin Ramli
Date Deposited: 30 Mar 2014 15:21
Last Modified: 02 Oct 2015 03:15
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1038/mp.2011.158
URI: http://psasir.upm.edu.my/id/eprint/24411
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