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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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BDNF and Sprouty2 expression in the frontal cortex of rats treated with haloperidol or olanzapine.Adult rats were treated with haloperidol (2 mg/kg) or olanzapine (10 mg/kg) through drinking water for 45 days, and (A) protein and (B) mRNA levels of BDNF and Sprouty2 in frontal cortex were estimated after the treatment. BDNF protein levels were measured by ELISA and Sprouty2 proteins levels were estimated by Western blot analysis. mRNA levels of both BDNF and Sprouty2 were estimated by qRT-PCR analysis. Open bars represent haloperidol-treated rats whereas filled bars represent olanzapine-treated rats. Values are expressed as fold change relative to vehicle-treated rats. *p<0.05, n = 10–12 per group.
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pone-0001784-g003: BDNF and Sprouty2 expression in the frontal cortex of rats treated with haloperidol or olanzapine.Adult rats were treated with haloperidol (2 mg/kg) or olanzapine (10 mg/kg) through drinking water for 45 days, and (A) protein and (B) mRNA levels of BDNF and Sprouty2 in frontal cortex were estimated after the treatment. BDNF protein levels were measured by ELISA and Sprouty2 proteins levels were estimated by Western blot analysis. mRNA levels of both BDNF and Sprouty2 were estimated by qRT-PCR analysis. Open bars represent haloperidol-treated rats whereas filled bars represent olanzapine-treated rats. Values are expressed as fold change relative to vehicle-treated rats. *p<0.05, n = 10–12 per group.

Mentions: In order to test the potential effect of antipsychotic medication, we evaluated mRNA as well as protein levels of BDNF and Spry2 in the frontal cortex of rats treated with haloperidol and olanzapine. Haloperidol treated rats showed significant reduction in mRNA (p = 0.03) as well as protein (p = 0.019) levels of BDNF, where as olanzapine treated rats showed significant increase in mRNA (p = 0.023) as well as protein (p = 0.045) levels of BDNF as compared to vehicle-treated rats (Figure 3). Interestingly, significant increase in Spry2 mRNA (p = 0.027) and protein (p = 0.02) expression was found in the frontal cortex of haloperidol-treated rats whereas olanzapine-treated rats showed significant decrease in Spry2 mRNA (p = 0.018) and protein (p = 0.041) expression as compared to vehicle-treated rats.


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

Pillai A - PLoS ONE (2008)

BDNF and Sprouty2 expression in the frontal cortex of rats treated with haloperidol or olanzapine.Adult rats were treated with haloperidol (2 mg/kg) or olanzapine (10 mg/kg) through drinking water for 45 days, and (A) protein and (B) mRNA levels of BDNF and Sprouty2 in frontal cortex were estimated after the treatment. BDNF protein levels were measured by ELISA and Sprouty2 proteins levels were estimated by Western blot analysis. mRNA levels of both BDNF and Sprouty2 were estimated by qRT-PCR analysis. Open bars represent haloperidol-treated rats whereas filled bars represent olanzapine-treated rats. Values are expressed as fold change relative to vehicle-treated rats. *p<0.05, n = 10–12 per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0001784-g003: BDNF and Sprouty2 expression in the frontal cortex of rats treated with haloperidol or olanzapine.Adult rats were treated with haloperidol (2 mg/kg) or olanzapine (10 mg/kg) through drinking water for 45 days, and (A) protein and (B) mRNA levels of BDNF and Sprouty2 in frontal cortex were estimated after the treatment. BDNF protein levels were measured by ELISA and Sprouty2 proteins levels were estimated by Western blot analysis. mRNA levels of both BDNF and Sprouty2 were estimated by qRT-PCR analysis. Open bars represent haloperidol-treated rats whereas filled bars represent olanzapine-treated rats. Values are expressed as fold change relative to vehicle-treated rats. *p<0.05, n = 10–12 per group.
Mentions: In order to test the potential effect of antipsychotic medication, we evaluated mRNA as well as protein levels of BDNF and Spry2 in the frontal cortex of rats treated with haloperidol and olanzapine. Haloperidol treated rats showed significant reduction in mRNA (p = 0.03) as well as protein (p = 0.019) levels of BDNF, where as olanzapine treated rats showed significant increase in mRNA (p = 0.023) as well as protein (p = 0.045) levels of BDNF as compared to vehicle-treated rats (Figure 3). Interestingly, significant increase in Spry2 mRNA (p = 0.027) and protein (p = 0.02) expression was found in the frontal cortex of haloperidol-treated rats whereas olanzapine-treated rats showed significant decrease in Spry2 mRNA (p = 0.018) and protein (p = 0.041) expression as compared to vehicle-treated rats.

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