2006 Fiscal Year Final Research Report Summary
The approach of improvement of neural network development as a new therapy for schizophrenia
| Project/Area Number |
17591224
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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 | Sapporo Medical University |
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Principal Investigator |
UKAI Wataru Sapporo Medical University, Dept of Neuropsychiatry, Assistant Professor, 医学部, 講師 (40381256)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Toshikazu Sapporo Medical University, Dept of Neuropsychiatry, Professor, 医学部, 教授 (50128518)
IKEDA Hiroshi Sapporo Medical University, Dept of Neuropsychiatry, Assistant Professor, 医学部, 講師 (30232193)
HASHIMOTO Eri Sapporo Medical University, Dept of Neuropsychiatry, Assistant Professor, 医学部, 講師 (30301401)
HASHIMOTO Ryota Sapporo Medical University, Dept of Mental Disorder Research, National Institute of Neuroscience, Section Chief, 疾病研究第三部, 室長 (10370983)
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| Project Period (FY) |
2005 – 2006
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| Keywords | schizophrenia / antipsychotic / neural stem cell / endoplasmic reticulum stress / neurogenesis / GRP78 / PERK |
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| Research Abstract |
Recent clinical neuroimaging studies have suggested that morphological brain changes occur and progress in the course of schizophrenia. Although the neurogenetic and neurotrophic effects of antipsychotics are considered to contribute to the prevention of reduction in brain volume, the cellular molecular mechanisms of action of antipsychotics have not yet been elucidated. We examined the effects of antipsychotics on the endoplasmic reticulum (ER) stress-induced damages of neurons and neural stem cells (NSCs) using cultured cells. In the neuronal cultures, the atypical antipsychotic olanzapine protected neurons from thapsigargin (1 μM)-induced injury. It was observed that a low concentration of thapsigargin (10 nM) that did not affect the neuronal survival could reduce neuronal differentiation of cultured NSCs, suggesting a role of ER stress in the differentiation function of NSCs. Treatment with olanzapine increased the neuronal differentiation suppressed by the exposure to thapsigargin (10 nM). The thapsigargin-induced ER chaperones, GRP78, which indicate the ER stress condition of the cell, were decreased by the treatment with the atypical antipsychotics olanzapine and quetiapine but not by the typical antipsychotic haloperidol. These results indicate that the amelioration of ER-stress might be involved in the cellular mechanisms of atypical antipsychotics to produce neuroprotective and neurogenetic actions in neurons and NSCs, suggesting potential roles of these drugs for treatment of schizophrenia.
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Research Products
(19 results)
