Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration.
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| Title: | Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration. |
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| Authors: | McOmish, C. E., Burrows, E., Howard, M., Scarr, E., Kim, D., Shin, H.-S., Dean, B., van den Buuse, M., Hannan, A. J. |
| Source: | Molecular Psychiatry. Jul2008, Vol. 13 Issue 7, p661-672. 12p. 7 Graphs. |
| Subjects: | Phospholipases, Animal models in research, Clozapine, Schizophrenia, Phenotypes, Drug administration |
| Abstract: | Phospholipase C-β1 (PLC-β1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-β1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-β1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenia-like symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-β1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene–environment interactions.Molecular Psychiatry (2008) 13, 661–672; doi:10.1038/sj.mp.4002046; published online 31 July 2007 [ABSTRACT FROM AUTHOR] |
| Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 32647183 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22McOmish%2C+C%2E+E%2E%22">McOmish, C. E.</searchLink><br /><searchLink fieldCode="AR" term="%22Burrows%2C+E%2E%22">Burrows, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Howard%2C+M%2E%22">Howard, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Scarr%2C+E%2E%22">Scarr, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Kim%2C+D%2E%22">Kim, D.</searchLink><br /><searchLink fieldCode="AR" term="%22Shin%2C+H%2E-S%2E%22">Shin, H.-S.</searchLink><br /><searchLink fieldCode="AR" term="%22Dean%2C+B%2E%22">Dean, B.</searchLink><br /><searchLink fieldCode="AR" term="%22van+den+Buuse%2C+M%2E%22">van den Buuse, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Hannan%2C+A%2E+J%2E%22">Hannan, A. J.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Jul2008, Vol. 13 Issue 7, p661-672. 12p. 7 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Phospholipases%22">Phospholipases</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+models+in+research%22">Animal models in research</searchLink><br /><searchLink fieldCode="DE" term="%22Clozapine%22">Clozapine</searchLink><br /><searchLink fieldCode="DE" term="%22Schizophrenia%22">Schizophrenia</searchLink><br /><searchLink fieldCode="DE" term="%22Phenotypes%22">Phenotypes</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+administration%22">Drug administration</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Phospholipase C-β1 (PLC-β1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-β1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-β1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenia-like symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-β1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene–environment interactions.Molecular Psychiatry (2008) 13, 661–672; doi:10.1038/sj.mp.4002046; published online 31 July 2007 [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/sj.mp.4002046 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 661 Subjects: – SubjectFull: Phospholipases Type: general – SubjectFull: Animal models in research Type: general – SubjectFull: Clozapine Type: general – SubjectFull: Schizophrenia Type: general – SubjectFull: Phenotypes Type: general – SubjectFull: Drug administration Type: general Titles: – TitleFull: Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: McOmish, C. E. – PersonEntity: Name: NameFull: Burrows, E. – PersonEntity: Name: NameFull: Howard, M. – PersonEntity: Name: NameFull: Scarr, E. – PersonEntity: Name: NameFull: Kim, D. – PersonEntity: Name: NameFull: Shin, H.-S. – PersonEntity: Name: NameFull: Dean, B. – PersonEntity: Name: NameFull: van den Buuse, M. – PersonEntity: Name: NameFull: Hannan, A. J. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 07 Text: Jul2008 Type: published Y: 2008 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 13 – Type: issue Value: 7 Titles: – TitleFull: Molecular Psychiatry Type: main |
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