Molecular biological study on the pathophysiology of bipolar disorders
| Project/Area Number |
15591206
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KUSUMI Ichiro Hokkaido Univ., Hokkaido Univ.Hospital, Lecturer, 病院, 講師 (30250426)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Katsuji Hokkaido Univ., Hokkaido Univ.Hospital, Instructor, 病院・助手 (70344512)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Bipolar disorder / Ca-ATPase pump (SERCA) / Proteinkinase C / Calmojurin / Thapsigargin / ATP2A2 gene / XBP1 gene / Ca mobilization / カルシウム / 血小板 / 小胞体ストレス反応 / セロトニン / TCI / NEO-FFI / ATP2A2遺伝子変異 / 一過性細胞質内カルシウム増加 / 容量依存性カルシウム流入 |
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| Research Abstract |
We examined thapsigargin (microsomal Ca-ATPase inhibitor)-induced transient intraplatelet calcium increase (TCI) and capcitative calcium entry (CCE) in the patients with bipolar disorder and major depressive disorder, and normal controls. There was no significant difference in thapsigargin-induced TCI or CCE among the three groups. However, in bipolar disorders, the inhibitory effect of proteinkinase C (PKC) stimulator on CCE was increased, and the stimulatory effect of PKC inhibitor on CCE was decreased. No significant differences in the effect of calmodulin inhibitor were observed among the three groups. These results suggest that the PKC function in bipolar disorders is compensatively enhanced to maintain the homeostasis of intracellular calcium (Ca) concentrations.
Enhanced Ca mobilization to various agonists in peripheral blood cells in one of a few confirmed biological markers for bipolar disorders. Recently, a polymorphism of XBP1, a pivotal gene in the endoplasmic reticulum stress response, was shown to contribute to the genetic risk factor for bipolar disorder. Thus, in this study, we examined the relationship between the XBP1 gene polymorphism and the Ca signaling in the platelets of healthy subjects. The present results suggest no significant difference in the basal Ca level or serotonin-induced Ca mobilization among normal subjects with -116C/C, C/G, G/G genotypes.
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Report
(3 results)
Research Products
(16 results)
