Phosphodiesterase 4 inhibition enhances the dopamine D1 receptor/PKA signaling cascade in frontal cortex.
| Project/Area Number |
22890228
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,068,000 (Direct Cost: ¥2,360,000、Indirect Cost: ¥708,000)
Fiscal Year 2011: ¥1,469,000 (Direct Cost: ¥1,130,000、Indirect Cost: ¥339,000)
Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
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| Keywords | ホスホジエステラーゼ / 統合失調症 / 大脳皮質 / DARPP-32 / ドーパミン / 認知機能障害 |
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| Research Abstract |
Alteration of dopamine neurotransmission in the prefrontal cortex, especially hypofunction of dopamine D1 receptors, contributes to psychotic symptoms and cognitive deficit in schizophrenia. D1 receptors signal through the cAMP/PKA second messenger cascade, which is modulated by phosphodiesterase(PDE) enzymes that hydrolyze and inactivate cyclic nucleotides. Though several PDEs are expressed in cortical neurons, the PDE4 enzyme family(PDE4A-D) has been implicated in the control of cognitive function. We revealed that PDE4, which is expressed in D1 receptor-positive cortical pyramidal neurons in layer VI, modulates the level of D1 receptor signaling in the frontal cortex, likely influencing cognitive function. These biochemical and behavioral actions of PDE4 inhibitors may contribute to the hypothesized antipsychotic actions of this class of compounds.
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Report
(3 results)
Research Products
(11 results)
