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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2007.1
- 수록면
- 353 - 360 (8page)
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Glycogen synthase kinase 3 (GSK3) was recently suggested to be a potential target of psychotropics used in psychiatric illn esses such as schizophrenia and bipolar disorder. Relevant studies have found that antipsychotic drugs regulate GSK3 activity via an increase in either in hibitory serine phospho-rylation or amount of GSK3 after acute or subchronic treatment. Recent evidence shows that GSK3 is regulated by dopaminergic or serotonergic systems implicated in the pathophysiology and treatment mechanisms of schizophrenia and bipolar disorder. Therefore, antipsychotics may regulate GSK3 via antagonizing dopaminergic or serotonergic activity. However, the signaling pathway that is involved in GSK3 regulation by dopaminergic or serotonergic established. Haloperidol is a typical antipsychotic with potent dopamine D2 receptor antagonism. Clozapine is an atypical antip-sychotic with potent serotonin 5HT2 receptor anta-gonism. We injected rats with haloperidol or clo-zapine and examined the phosphorylation and amount of GSK3α/β and its well-known upstream regulators Akt and Dvl in the rat frontal cortex by Western blotting. Both haloperidol and clozapine induced Ser21/9 phosphorylation of GSK3 α/β. Halo-peridol increased the Ser473 phosphorylation of Akt transiently, whereas clozapine maintained the in-phorylation and amount of Dvl, whereas clozapine increased both phosphorylation and the amount of Dvl. Our results suggest that GSK3 activity may be regulated by both typical and atypical antipsychotics and that Akt or Dvl, depending on the D2- or 5HT2- receptor antagonism properties of typical and aty-pical antipsychotics, mediate the regulation differently.
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등록된 정보가 없습니다.
참고문헌 (26)
참고문헌 신청
Ahmad-Annuar A / 2006 / Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assem-bly and neurotransmitter release 174 : 127 ~ 139
Alimohamad H / 2005a / Antip-sychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum 57 : 533 ~ 542
Alimohamad H / 2005b / The effects of antipsychotics on beta-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats 95 : 513 ~ 525
Ananth J / 2004 / Drug therapy in schizo-phrenia 10 : 2205 ~ 2217
Beaulieu JM / 2004 / Lithium antagonizes dop-amine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade 101 : 5099 ~ 5104
Alimohamad H / 2005a / Antip-sychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum 57 : 533 ~ 542
Alimohamad H / 2005b / The effects of antipsychotics on beta-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats 95 : 513 ~ 525
Ananth J / 2004 / Drug therapy in schizo-phrenia 10 : 2205 ~ 2217
Beaulieu JM / 2004 / Lithium antagonizes dop-amine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade 101 : 5099 ~ 5104
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