2002 Fiscal Year Final Research Report Summary
Roles of neuronal cellular signaling and plasticity disturbances in the pathophysiology of affective disorders and schizophrenia
| Project/Area Number |
13671023
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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 |
OZAWA Hiroki Dept.of Neuropsychiatry School of Medicine, Sapporo Medical University, associate professor, 医学部, 助教授 (50260766)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Toshikazu Dept.of Neuropsychiatry School of Medicine, Sapporo Medical University, Professor, 医学部, 教授 (50128518)
SASAKI Nobuyuki Dept.of Neuropsychiatry School of Medicine, Sapporo Medical University, Assistant, 医学部, 兼務助手 (60315497)
IKEDA Hiroshi Dept.of Neuropsychiatry School of Medicine, Sapporo Medical University, asisstant professor, 医学部, 講師 (30232193)
SOHMA Hitoshi Dept.of Biochemistry School of Medicine, Sapporo Medical University, associate professor, 医学部, 助教授 (70226702)
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| Project Period (FY) |
2001 – 2002
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| Keywords | schizophrenia / affective disorder / cAMP / CREB / development sprouting / postmortem human brain / neural stem cell |
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| Research Abstract |
The schizophrenia and the affective disorders have been established independent pathophysiological diseases as major neuropsychiatric disorders. However, recent studies demonstrate the difficulty of discrimination of the depressive symptoms and negative symptoms in the schizophrenic patients, and some reports indicate that these illnesses can have some overlapped symptoms each other. In addition, it is also suggested that recently depveloped anthipsychotics showed high affinity for the 5-HT_<2A> receptors and had pharmachological properties in common with antidepressants. Although, these symptomatological and pharmachological similarities and differences of schizophrenia and depression may be resulted from the neuronal plasticity changes mediated by the alternation of intracellular signal transduction mechanisms, there are few studies to clarify the molecular basis of the illness itself using postmortem human brains. Therefore we investigated that 1) cAMP-CREB system and the distributi
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onal changes of Gsα in the cytoplasmic membranes in the postmortem human brains, 2) genes researches related to the neuronal development and sprouting in the early postnatal stages of human brains, and 3) roles of neural stem cells on the neuropsychiatric disorders.
The functional imbalances of cAMP-CREB signalling were observed in the frontal cortex from postmortem human brains, with disturbance in depression, while hypofunction in schizophrenia. The cAMP related gene (CBP), trophic factor related gene (human insulin-like growth factor binding protein 5) and apoptosis related gene (caspases) expression changes were recognized in the early developing human frontal cortex. Moreover, we demonstrated the isolation and successive propagation of neural stem cells from human post mortem brain tissues and progressive effects of cAMP signaling stimulating agents and neurotrophic factos on neural stem cell differentiation in vitro. Altogether, progress of novel drugs development that modulates cAMP-CREB systems and neural stem cell therapy may lead to new insights treating neuropsychiatric disorders, and it is important to develop the biological markers in peripheral tissues related to their observations. Less
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[Publications] Yamamoto, M., Pohli, S., Durany, N., Ozawa, H., Saito, T, Boissl, K.W., Zochling, R., Riederer, P., Boning, J., Gotz, M.E.: "Increased levels of calcium-sensitive adenylyl cyclase subtypes in the signaling in the human addictive brain"Brain Research. 895. 233-237 (2001)
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[Publications] Sasaki, R., Sasaki, N., Ozawa, H., Ikeda, H., Nakano, N., Saito, T.: "Use experience of milnacipran-Clinical effectiveness on the effect over somatic symptoms-"Jpn.J.Cllinical.Psychopharmacology. 5. 93-101 (2002)
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[Publications] Yamamoto, M., Yamada, S., Ozawa, H., Toki, S., Choei, H., Saito, T.: "Cyclic AMP-responsive element binding protein in the postmortem frontal cortex of depressed patients and controls"Jpn.J.Annual Report of the Pharmacopsychiatry Research Foundation. 34. 237-241 (2002)
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「研究成果報告書概要(欧文)」より
