| Project/Area Number |
16390328
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | RIKEN |
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Principal Investigator |
KATO Tadafumi RIKEN, Aging and Psychiatric Research Group, Group Director, 老化・精神疾患研究グループ, グループディレクター (30214381)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥13,900,000 (Direct Cost: ¥13,900,000)
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| Keywords | bipolar disorder / endoplasmic reticulum stress / XBP1 / neurons / 神経発達 / 神経可塑性 / x-box binding protein / 小胞体ストレス反応 |
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| Research Abstract |
High concordance rate of bipolar disorder in monozygotic (MZ) twins (approximately 70%) suggests the role of genetic factors in this disorder. We performed DNA microarray analysis in the lymphoblastoid cell lines obtained from two pairs of MZ twins discordant for bipolar disorder. We found that two genes, XBP1 and GRP78 (HSPA5), both of which have a pivotal role in endoplasmic reticulum (ER) stress signaling, were commonly down-regulated. XBP1 is located at 22q12, the common linkage locus for bipolar disorder and schizophrenia. GRP78 is regulated by XBP1, and induced by valproate. Thus, we further analyzed the roles of XBP1 and GRP78 in the pathophysiology of bipolar disorder. Response of XBP 1 and GRP78 to ER stress was smaller in patients with bipolar disorder compared with controls. We found a functional polymorphism in the promoter of XBP1, named -116C/G. The functional disturbance caused by -116G was improved by valproate. We found that XBP1 is located throughout the neuron and transport the neuroplastic signals from dendrite to the nucleus. By DNA microarray analysis, XBP1 was found to regulate WFS 1. These findings suggest that XBP1 plays a role in neuroplastic changes and XBP1-WFS1 pathway plays a role in mental disorders.
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