2007 Fiscal Year Final Research Report Summary
Assocation between PICK1 gene and schizophrenia
| Project/Area Number |
18591288
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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 | Tottori University |
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Principal Investigator |
MAEDA Kazuhisa Tottori University, Psychiatry, Junior Associate Professor (40283981)
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| Project Period (FY) |
2006 – 2007
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| Keywords | PICK1 / schizophrenia / D-serine |
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| Research Abstract |
D-serine is an endogenous cagonist of the N-methy-D-aspartate subtype of glutamate receptor. Genetic association studies have implicated genes cording for enzymes associated with D-serine metabolism in schizophrenia (SZ) and bipolar disorder. We have identified and characterized protein interacting with C-kinase (PICK1) as a protein interacter of the D-serine synthesizing enzyme, serine racemase (SR). We also have observed an association of the PICK1 gene with SZ, which is more prominent in disorganized group of SZ. In this study, we explored the role of PICK1 for D-serine synthesis in cell culture models and in vivo transfection of PICK1 into the brain of animals. Furthermore, we also explored the association between PICK1 and neuropsychological markers.
First, we use HEK293 cells, which have almost no endogenous SR. In HEK293 cells transfected with wildtype PICK1, SR, or both, we observed and increased ratio of D-serine to SR in cells expressing both SR and PICK1 compared with SR alone. The SR mutant K27A/D28A, which cannot interact with each other, abolished the increase in D-serine. Reducing PICK1 expression using siRNA to PICK1 also prevented the increase in D-serine production. Next, we examined the effect of overtransfection of PICK1 for animals in vivo. We found the tendency of increasing of D-serine in the transfected region of the brains, but it was not significant. Next, we investigated the association of PICK1 polymorphisms with anitisacade eye movements in SZ patients, but we could not find significant result from our subjects. These results suggest that PICK1 may be involved in increasing D-serine levels because of its interaction with SR. Further research is needed to explore the association between PICK1 and neuropsychological markers in SZ.
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[Journal Article] Modulation of D-serine levels in brains of mice lacking PICKI2008
Author(s)
Hikida, T., Mustafa, AK., Maeda, K., Fujii, K., Barrow, RK., Saleh, M., Huganir, RL., Snyder, SH., Hashimoto, K., Sawa, A
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Journal Title
Biol Psychiatry 63
Pages: 997-1000
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of PICK1 on D-serine synthesis and schizophrenia2006
Author(s)
Hikida, T., Mustafa, AK., Hashimoto, K., Fujii, K., Maeda, K., Ujike, H., Huganir, RL., Snyder, SH., Sawa, A
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Journal Title
NEUROSCIENCE RESEARCH 55
Pages: S213-S213
Description
「研究成果報告書概要(欧文)」より
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[Presentation] PICK1 polmorphisms and association with methamphetamine psychosis2006
Author(s)
Matsuzawa, D., Hashimoto, K., Miyatake, Y., Shirayama, Y., Shimizu, E., Maeda, K., Suzuki, Y., Mashimo, Y., Sekine, Y., Inada, T., Ozaki, N., Iwata, T., Harano, M., Komiyama, T., Yamada, M., Sora, I., Ujike, H., Hata, A., Sawa, A., Iyo, M
Organizer
36th Annual Meeting of the Society for Neuroscience
Place of Presentation
Atlanta
Year and Date
2006-10-16
Description
「研究成果報告書概要(欧文)」より
