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

Pillai A - PLoS ONE (2008)

Bottom Line: The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Health Behavior, Medical College of Georgia, Medical Research Service Line, Veterans Affairs Medical Center, Augusta, Georgia, United States of America. apillai@mail.mcg.edu

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.

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Normalized Sprouty2 mRNA expression in schizophrenia, bipolar and control subjects.Values are expressed as mean±SEM. The number of individuals per sample is indicated within each bar. Sprouty2 expression is significantly low in schizophrenia and bipolar subjects as compared to control subjects. Level of significance as compared to control subjects is shown above each bar.
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pone-0001784-g001: Normalized Sprouty2 mRNA expression in schizophrenia, bipolar and control subjects.Values are expressed as mean±SEM. The number of individuals per sample is indicated within each bar. Sprouty2 expression is significantly low in schizophrenia and bipolar subjects as compared to control subjects. Level of significance as compared to control subjects is shown above each bar.

Mentions: A significant reduction in mean Spry2 mRNA levels was observed in the schizophrenia (33%; p = 0.0098) and bipolar groups (46%; p = 0.003) compared to the control group (Figure 1). Similarly, mean BDNF mRNA levels were significantly reduced in schizophrenia group (34%; p = 0.0027) and bipolar group (40%; p = 0.003) as compared to the control group (Figure 2). To study the relationship between Spry2 and BDNF, Pearson's correlation was performed in schizophrenia group, bipolar group and control group (Table 3). Significant high correlation between Spry2 and BDNF mRNA expression levels was found in schizophrenia group (p = 0.01), bipolar group (p = 0.02) and control group (p = 0.016).


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

Pillai A - PLoS ONE (2008)

Normalized Sprouty2 mRNA expression in schizophrenia, bipolar and control subjects.Values are expressed as mean±SEM. The number of individuals per sample is indicated within each bar. Sprouty2 expression is significantly low in schizophrenia and bipolar subjects as compared to control subjects. Level of significance as compared to control subjects is shown above each bar.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2262156&req=5

pone-0001784-g001: Normalized Sprouty2 mRNA expression in schizophrenia, bipolar and control subjects.Values are expressed as mean±SEM. The number of individuals per sample is indicated within each bar. Sprouty2 expression is significantly low in schizophrenia and bipolar subjects as compared to control subjects. Level of significance as compared to control subjects is shown above each bar.
Mentions: A significant reduction in mean Spry2 mRNA levels was observed in the schizophrenia (33%; p = 0.0098) and bipolar groups (46%; p = 0.003) compared to the control group (Figure 1). Similarly, mean BDNF mRNA levels were significantly reduced in schizophrenia group (34%; p = 0.0027) and bipolar group (40%; p = 0.003) as compared to the control group (Figure 2). To study the relationship between Spry2 and BDNF, Pearson's correlation was performed in schizophrenia group, bipolar group and control group (Table 3). Significant high correlation between Spry2 and BDNF mRNA expression levels was found in schizophrenia group (p = 0.01), bipolar group (p = 0.02) and control group (p = 0.016).

Bottom Line: The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Health Behavior, Medical College of Georgia, Medical Research Service Line, Veterans Affairs Medical Center, Augusta, Georgia, United States of America. apillai@mail.mcg.edu

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.

Show MeSH
Related in: MedlinePlus