Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.

Hdl Handle:
http://hdl.handle.net/10675.2/101
Title:
Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.
Authors:
Pillai, Anilkumar
Abstract:
BACKGROUND: Current theories on the pathophysiology of schizophrenia suggest altered brain plasticity such as decreased neural proliferation and migration, delayed myelination, and abnormal synaptic modeling, in the brain of subjects with schizophrenia. Though functional alterations in BDNF, which plays important role in neuroplasticity, are implicated in many abnormalities found in schizophrenia, the regulatory mechanism(s) involved in the abnormal signaling of BDNF in schizophrenia is not clear. The present study investigated whether Sprouty2, a regulator of growth factor signaling, is abnormally expressed in schizophrenia, and is associated with the changes in BDNF mRNA in this disorder. The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats. METHODS AND FINDINGS: Sprouty2 and BDNF gene expression were analyzed in dorsolateral prefrontal cortex samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA in 100 individuals (35 with schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls) showed significantly decreased expression of Sprouty2 and BDNF in both schizophrenia and bipolar disorder. Moreover, a significant correlation between these two genes existed in control, schizophrenia and bipolar subjects. Long-term treatment with antipsychotic drugs, haloperidol and olanzapine, showed differential effects on both Sprouty2 and BDNF mRNA and protein levels in the frontal cortex of rats. CONCLUSION: These findings demonstrating decreased expression of Sprouty2 associated with changes in BDNF, suggest the possibility that these decreases are secondary to treatment rather than to factors that are significant in the disease process of either schizophrenia and/or bipolar disorder. Further exploration of Sprouty2-related signal transduction pathways may be helpful to design novel treatment strategies for these disorders.
Citation:
PLoS ONE. 2008 Mar 12; 3(3):e1784
Issue Date:
12-Mar-2008
URI:
http://hdl.handle.net/10675.2/101
DOI:
10.1371/journal.pone.0001784
PubMed ID:
18335055
PubMed Central ID:
PMC2262156
Type:
Journal Article
ISSN:
1932-6203
Appears in Collections:
Department of Psychiatry and Health Behavior: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorPillai, Anilkumaren_US
dc.date.accessioned2010-09-24T22:03:19Z-
dc.date.available2010-09-24T22:03:19Z-
dc.date.issued2008-03-12en_US
dc.identifier.citationPLoS ONE. 2008 Mar 12; 3(3):e1784en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid18335055en_US
dc.identifier.doi10.1371/journal.pone.0001784en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/101-
dc.description.abstractBACKGROUND: Current theories on the pathophysiology of schizophrenia suggest altered brain plasticity such as decreased neural proliferation and migration, delayed myelination, and abnormal synaptic modeling, in the brain of subjects with schizophrenia. Though functional alterations in BDNF, which plays important role in neuroplasticity, are implicated in many abnormalities found in schizophrenia, the regulatory mechanism(s) involved in the abnormal signaling of BDNF in schizophrenia is not clear. The present study investigated whether Sprouty2, a regulator of growth factor signaling, is abnormally expressed in schizophrenia, and is associated with the changes in BDNF mRNA in this disorder. The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats. METHODS AND FINDINGS: Sprouty2 and BDNF gene expression were analyzed in dorsolateral prefrontal cortex samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA in 100 individuals (35 with schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls) showed significantly decreased expression of Sprouty2 and BDNF in both schizophrenia and bipolar disorder. Moreover, a significant correlation between these two genes existed in control, schizophrenia and bipolar subjects. Long-term treatment with antipsychotic drugs, haloperidol and olanzapine, showed differential effects on both Sprouty2 and BDNF mRNA and protein levels in the frontal cortex of rats. CONCLUSION: These findings demonstrating decreased expression of Sprouty2 associated with changes in BDNF, suggest the possibility that these decreases are secondary to treatment rather than to factors that are significant in the disease process of either schizophrenia and/or bipolar disorder. Further exploration of Sprouty2-related signal transduction pathways may be helpful to design novel treatment strategies for these disorders.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntipsychotic Agents / therapeutic useen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBipolar Disorder / drug therapy / metabolismen_US
dc.subject.meshBrain-Derived Neurotrophic Factor / genetics / metabolismen_US
dc.subject.meshDNA Primersen_US
dc.subject.meshHumansen_US
dc.subject.meshIntracellular Signaling Peptides and Proteins / genetics / metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshPrefrontal Cortex / metabolismen_US
dc.subject.meshRNA, Messenger / geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSchizophrenia / drug therapy / metabolismen_US
dc.titleDecreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.en_US
dc.typeJournal Articleen_US
dc.identifier.pmcidPMC2262156en_US
dc.contributor.corporatenameDepartment of Psychiatry and Health Behavioren_US
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