| Project/Area Number |
16591139
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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 | Chiba University (2005)
Tottori University (2004) |
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Principal Investigator |
SHIRAYAMA Yukihiko Chiba University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究院, 講師 (20261191)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Kazuhisa Tottori University, Hospital, Assistant Professor, 医学部附属病院, 講師 (40283981)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | PICK1 / Schizophrenia / Animal model / Gria / D-serine / Phencyclidine / Rat / Prefrontal cortex / D-セリン / グルタミン酸 / GABA |
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| Research Abstract |
This study is to examine a role of protein interacting with C-kinase (PICK1 gene) in schizophrenia. As for animal models of schizophrenia, SD rats were administered phencyclidine (5 mg/kg, two times a day, ip) for 7 days and were kept for 7 days of withdrawal. Repeated phencyclidine administered rats failed to demonstrate any changes in locomotion to noble situation in a noble test. However, this animal model showed enhanced sensitivity to re-administration of phencyclidine (10 mg/kg or 1 mg/kg, ip). Furthermore, this animal model showed super-sensitivity to cocaine (15 mg/kg, ip) injection. However, in a passive avoidance based learning paradigm, phencyclidine-treated rats did not show any deficits in comparison with saline-treated rats. For a while, phencyclidine-treated animals showed a decrease in expression of PICK1 protein expression in the ventral portion of the nucleus accumbens and striatum.
Next, we attempted direct in vivo protein transduction by microinjecting PICK1 gene with hemagglutinating virus of Japan envelope (HVJ-E) vector into the medial prefrontal cortex. Nine days after microinjection, rats were killed. Identification of D-serine and L-serine was done using high performance liquid chromatography (HPLC). Normal rats showed an elevation of D-serine in the prefrontal cortex after the microinjection of PICK1 gene.
Future study is planed to examine the effects of microinjection of PICK1 gene with HVJ-E vector into the medial prefrontal cortex of phencyclidine-treated rats using the above behavioral paradigm (open field test).
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