| Project/Area Number |
15209036
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
MORI Norio Hamamatsu University School of Medicine, Psychiatry and Neurology, Professor, 医学部, 教授 (00174376)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEI Noriyoshi Hamamatsu University School of Medicine, Psychiatry and Neurology, Associate Professor, 医学部, 助教授 (80206937)
MINABE Yoshio Hamamatsu University School of Medicine, Psychiatry and Neurology, Lecturer, 医学部附属病院, 講師 (60181947)
NAKAMURA Kazuhiko Hamamatsu University School of Medicine, Psychiatry and Neurology, Lecturer, 医学部附属病院, 講師 (80263911)
SATO Kohji Hamamatsu University School of Medicine, Anatomy, Professor, 医学部, 教授 (80235340)
岩田 泰秀 浜松医科大学, 医学部, 助手 (10285025)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2005: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2004: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2003: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
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| Keywords | schizophrenia / neural stem cell / animal model / LIFR knockout mice / VLDLR / ApoER2 / x-irradiation / peripheral biological markers / 放射線 / LIFR (leukemia inhibitory factor receptor) / VLDLR (very low density lipoprotein receptor) / ApoER2 (apolipoprotein E receptor type 2) |
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| Research Abstract |
1.An animal model for schizophrenia based on hypothesis of neural stem cell dysfunction :
(1)Male Sprague-Dawley rats were irradiated to the forebrain using 6 fractions of 5 Gy. After 12 weeks, neural stem cells (BrdU positive cells) were diminished in both subventricular zone and hippocampal dentate gyrus subgranular zone. A significant increase in locomotor activity after administration of methamphetamine (MAP) (2 mg/kg i.p.) or MK-801 (0.2 mg/kg i.p.) was observed. Acoustic prepulse inhibition and social behaviors of the irradiated rats were significantly decreased. Moderate impairments of spatial working memory and reference memory assessed by Morris water maze were found in the model rats. (2)It has been reported that LIFR-deficient mice revealed a reduction in the number of adult neural stem cells. Locomotor activity induced by MAP was significantly increased in the LIFR knockout mice. However, behavioral change after MK-801 or prepulse inhibition of startle responces was not obse
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rved. (3)We transplanted embryonic neural precursor cells (NPCs) into the bilateral ventricles and the dentate gyri of the irradiated rats at 3 months after irradiation. The MAP-induce hyperactivity was not ameliorated at 4 weeks after the NPCs transplantation.
2.Peripheral biological markers for schizophrenia :
Reelin is a secretory protease with major roles in neurodevelopment and plasticity. A reduction of reelin expression is one of the most robust molecular findings in schizophrenia. Apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR) are reelin receptors. In search for peripheral biological markers for schizophrenia we have investigated mRNA levels of ApoER2 and VLDLR in peripheral blood lymphocytes of drug naive patients with schizophrenia, mood disorder and healthy controls. We observed a significant decrease of VLDLR mRNA levels in schizophrenia, but not those in mood disorder, compared with controls. A significant decrease in the ApoER2 mRNA level was found only in mood disorder. Less
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