2006 Fiscal Year Final Research Report Summary
The role of endoplasmic reticulum stress response in the pathophysiology of bipolar disorder
| Project/Area Number |
17591192
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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 University, Hokkaido University Hospital, Lec., 大学病院, 講師 (30250426)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Katsuji Hokkaido University, Hokkaido University Hospital, Inst., 大学病院, 助手 (70344512)
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| Project Period (FY) |
2005 – 2006
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| Keywords | ER stress response / Bipolar disorder / XBP1 gene / Personality traits / Lithium / Valproate / SERCA / Protein kinase C |
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| Research Abstract |
Recently, a functional polymorphism (-116C/G) of the XBP1 gene was reported to contribute to the genetic risk factor for bipolar disorder (BPD). Moreover, the endoplasmic reticulum (ER) stress response were impaired in cultured lymphocytes from BPD patients with G allele and only valproate rescued the impairment of the ER stress response among three major mood stabilizers. In this context, it is likely that BPD patients with different genotype respond differently to mood stabilizers. Therefore, we investigated the association of-116C/G polymorphism and lithium response in patients with BPD. We found that lithium treatment is more effective in Japanese BPD patients with-116C allele carrier than in those with G allele homozygous.
Disturbed intracellular calcium (Ca^<2+>) homeostasis has been implicated in BPD, which mechanisms may be involved in the dysregulation of protein kinase C (PKC) and calmodulin systems. In this study, we investigated a transient intracellular Ca^<2+> increase ind
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uced by thapsigargin, a inhibitor of sarco/endoplasmic reticulum Ca^<2+>-ATPase pump (SERCA), and a capacitative Ca^<2+> entry followed by addition of extracellular Ca^<2+>, in the presence or absence of PKC/calmodulin modulators in the platelets of healthy subjects in order to elucidate the role of SERCA in Ca^<2+> homeostasis and to assess how both PKC and calmodulin systems regulate the two Ca^<2+> responses. Moreover, we also examined the thapsigargin-elicited transient Ca^<2+> increase and capacitative Ca2+ entry in patients with mood disorders. PKC and calmodulin systems have opposite regulatory effects on the transient C^<2+> increase and capacitative Ca2+ entry in the platelets of normal subjects. The inhibitory effect of PKC activation on capacitative Ca^<2+> entry is significantly increased and the stimulatory effect of PKC inhibition is significantly decreased in BPD compared to major depressive disorder and normal controls. These results suggest the possibility that increased PKC activity may activate the inhibitory effect of capacitative Ca^<2+> entry in BPD. Less
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Research Products
(10 results)
