2007 Fiscal Year Final Research Report Summary
Investigation of fragility factors related to cognitive dysfunction and neurodegeneration in animal models of schizophrenia
| Project/Area Number |
17390018
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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 |
Biological pharmacy
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| Research Institution | Meijo University (2007)
Nagoya University (2005-2006) |
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Principal Investigator |
NABESHIMA Toshitaka Meijo University, Faculty of Pharmacy, Professor (70076751)
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| Co-Investigator(Kenkyū-buntansha) |
NODA Yukihiro Meijo University, Faculty of Pharmacy, Professor (90397464)
NITTA Atsumi Nagoya University, Grandate School of Medicine, Associate Professor (20275093)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Phencyclidine / Emotional Deficit / Cognitive Deficit / Disrupted-in-schizonhrenia 1 / Neurodevelopment / Prefrontal Cortex / NMDA Receptor / Schizophrenia |
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| Research Abstract |
We attempted to investigate the molecular mechanisms of emotional and cognitive deficits in schizophrenia-like animal models based on dysfunction hypothesis of glutamatergic systems and neurodevelopment. The mice treated with phencyclidine (PCP: a non-competitive NMDA receptor antagonist) repeatedly exhibited emotional and cognitive deficits. The repeated PCP treatment induced an impaired NMDA-CaMKII signaling and decreased spontaneous extracellular glutamate levels in the prefrontal cortex(PFC).
We have found that the mice which via in utero gene transfer achieved selective knockdown of DISC1 in pyramidal neurons of the frontal cortex only during the development, showed maturation-dependent deficits in the mesocortical dopaminergic projections and associated behavioral changes relevant to schizophrenia after puberty. This strategy allows simultaneous manipulation of multiple factors during development in a temporally and spatially specific manner and could be applied generally to exploring disease pathways for major mental illnesses with developmental origins.
To examine the changes in protein expression after repeated PCP treatment in PFC of mice, we performed proteomic analysis by using fluorescence two-dimensional difference gel electrophoresis (2D-DIGE). Changes in the relative abundance of 9 protein spots were observed in the PCP-treated mice compared to the saline-treated control mice. Seven spots exhibited an increase, but, 2 protein spots were decreased in the PCP-treated mice when compared to the saline-treated mice. Seven spots identified by liquid chromatographyttandem mass spectrometry were grouped into three functional classes; cell signaling (5 spots), protein degradation (1 spot) and energy metabolism (1 spot). These results suggest that altered protein expressions in the PFC may involve in the molecular mechanisms underlying the schizophrenia-like symptoms in repeated PCP-treated mice.
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Research Products
(134 results)
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[Presentation] Involvement of glutamatergic system in emotional deficits in repeated phencyclidine-treated mice2005
Author(s)
Murai, R., Noda, Y., Mouri, A., Nitta, A., Furukawa, H. and Nabeshima, T.
Organizer
Taiwan-Japan Joint Seminar
Place of Presentation
Nagoya
Year and Date
2005-08-08
Description
「研究成果報告書概要(和文)」より
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