Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency.
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 s...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English English |
| Published: |
Nature Publishing Group
2012
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/24411/1/Neurodevelopmental%20and%20neuropsychiatric%20behaviour%20defects%20arise%20from%2014.pdf |
| _version_ | 1825925566511972352 |
|---|---|
| author | Cheah, Pike See Ramshaw, H. S. Thomas, P. Q. Toyo-oka, K. Xu, X. Martin, S. Coyle, P. Guthridge, M. A. Stomski, F. Van den Buuse, M. Wynshaw-Boris, A. Lopez, A. F. Schwarz, Q. P. |
| author_facet | Cheah, Pike See Ramshaw, H. S. Thomas, P. Q. Toyo-oka, K. Xu, X. Martin, S. Coyle, P. Guthridge, M. A. Stomski, F. Van den Buuse, M. Wynshaw-Boris, A. Lopez, A. F. Schwarz, Q. P. |
| author_sort | Cheah, Pike See |
| collection | UPM |
| description | 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. |
| first_indexed | 2024-03-06T07:59:47Z |
| format | Article |
| id | upm.eprints-24411 |
| institution | Universiti Putra Malaysia |
| language | English English |
| last_indexed | 2024-03-06T07:59:47Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | upm.eprints-244112015-10-02T03:15:48Z http://psasir.upm.edu.my/id/eprint/24411/ Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. Cheah, Pike See Ramshaw, H. S. Thomas, P. Q. Toyo-oka, K. Xu, X. Martin, S. Coyle, P. Guthridge, M. A. Stomski, F. Van den Buuse, M. Wynshaw-Boris, A. Lopez, A. F. Schwarz, Q. P. 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. Nature Publishing Group 2012 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/24411/1/Neurodevelopmental%20and%20neuropsychiatric%20behaviour%20defects%20arise%20from%2014.pdf 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 http://www.nature.com/mp/index.html 10.1038/mp.2011.158 English |
| spellingShingle | Cheah, Pike See Ramshaw, H. S. Thomas, P. Q. Toyo-oka, K. Xu, X. Martin, S. Coyle, P. Guthridge, M. A. Stomski, F. Van den Buuse, M. Wynshaw-Boris, A. Lopez, A. F. Schwarz, Q. P. Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. |
| title | Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. |
| title_full | Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. |
| title_fullStr | Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. |
| title_full_unstemmed | Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. |
| title_short | Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. |
| title_sort | neurodevelopmental and neuropsychiatric behaviour defects arise from 14 3 3ζ deficiency |
| url | http://psasir.upm.edu.my/id/eprint/24411/1/Neurodevelopmental%20and%20neuropsychiatric%20behaviour%20defects%20arise%20from%2014.pdf |
| work_keys_str_mv | AT cheahpikesee neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT ramshawhs neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT thomaspq neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT toyookak neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT xux neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT martins neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT coylep neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT guthridgema neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT stomskif neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT vandenbuusem neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT wynshawborisa neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT lopezaf neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency AT schwarzqp neurodevelopmentalandneuropsychiatricbehaviourdefectsarisefrom1433zdeficiency |