Study on the activation of endogeneous neural stem cells as a new therapeutic interention for depression
| Project/Area Number |
18591301
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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 |
HASHIMOTO Eri Sapporo Medical University, Dept of Neuropsychiatry, Associate Professor (30301401)
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| Co-Investigator(Kenkyū-buntansha) |
UKAI Wataru Sapporo Medical University, Dept. of Neuropsychiatry, Assistant Professor (40381256)
IKEDA Hiroshi Hokkaido Bunkyo University, Faculty of Human Science, Professor (30232193)
YAMADA Misa National Center of Neurology and Psychiatry, Dept of Psychogeriatrics, Research Fellow (10384182)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | neuroscience / brain / depression / neural stem cell / antidepressant / neurogenesis / ER stress / cultured cell |
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| Research Abstract |
Many studies suggest the stressful events possibly promote neurochemical changes in the brain and induce the abnormality of neurogenesis that may be involved in the pathogenesis of depression. We previously have indicated the promotive effects of antidepressants on the neural stem cell (NSC) differentiation. In the present study, we investigated the effect of antidepressants on the NSC functional change induced by ER stress, and analyzed the cellular regulatory mechanism including the trophic factor signaling and NRSF which acts as a transcriptional repressor of neuronal genes in the terminal stage of NSC differentiation. We prepared NSCs from rat embryos and evaluated neuronal differentiation by using cell counting and ELISA. ER stress suppressed neuronal differentiation even at lower concentrations that did not affect the survival of NSCs. Antidepressants promoted neuronal differentiation of NSCs and reduced binding activity of NRSF against ER stress, while ERK signaling reduction decreased neuronal differentiation and activated NRSF binding activity. These results suggest that the alteration of NRSF binding activity through ER stress and/or ERK signaling underlies the mechanism of NSC dysfunction in depression and one of the critical cellular mechanisms of the effects of antidepressants. We also tried to visualize the transplanted NSCs in the brain of a psychiatric disease model rat using the marked NSCs. The transplanted cells were detected in wide areas of brain and were greater in number in the brains of the model rat group to the control group. With the cDNA microarray on which antidepressant related genes (ADRGs) were spotted, we found the expression of some of the ADRGs including ADRG#116 were related to neural differentiation and development. These results suggest some candidate genes and molecules as the novel therapeutic targets by activating intrinsic NSCs.
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Report
(3 results)
Research Products
(109 results)
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[Journal Article] Advances2006
Author(s)
Yamada M, et. al.
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Journal Title
Neuroregulation and Neuroprotection, VSP Brill Academic Publishers
Pages: 315-330
Description
「研究成果報告書概要(和文)」より
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[Presentation] Endoplasmic reticulum stress in psychiatric disorder. < ; Symposium> ; Organelle stress in neuropsychiatric disorder2008
Author(s)
Saito, T., Ukai, W., Hashimoto E., Ishii, T., Yoshinaga, T., Tateno, M., Saito, S. T
Organizer
Collegium International Neuro-Psychopharmacologicum Pacific-Asia Regional Meeting
Place of Presentation
Kuala Lumpur, Malaysia
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The effects of antidepressants on the regulation of neuronal phenotype specific differentiation in vitro2007
Author(s)
Ukai, W., Imai, T., Ishii, T., Yoshinaga, T., Ono, T., Saito, S., Hashimoto., E, Saito, T
Organizer
World Psychiatric Association Regional Meeting
Place of Presentation
Seoul, Korea
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Neural stem cell transplantation in a model of fetal alcohol effects2007
Author(s)
Yoshinaga, T., Ukai, W., Ishii, T., Ono, T., Tateno, M., Hashimoto, E., Saito, S., Saito T
Organizer
Joint Meeting of the 29th Annual Meeting of Japanese Society of Biological Psychiatry and the 37th Annual Meeting of Japanese Society of Neuropsychopharmacology
Place of Presentation
Sapporo, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Direct/indirect mechanism of neuroprotection by neural stem cell against NMDA antagonist-induced damage2007
Author(s)
Ono, T., Ukai, W., Yoshinaga, T., Ishii, T., Watanabe, K., Tateno, M., Hashimoto, E., Saito, T
Organizer
Joint Meeting of the 30th Annual Meeting of the Japan Neuroscience Society and the 50th Annual Meeting of the Japanese Society for Neurochemistry and the 17th Annual Meeting of the Japanese Neural Network Society
Place of Presentation
Yokohama, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ethanol-induced brain injury : therapeutic potential of neurogenesis for recovery from ethanol-induced damage of neuronal network. < ; Symposium> ; ESBRA-ISABRA joint meeting : Alcohol and organ damage2007
Author(s)
Hashimoto, E., Yoshinaga, T., Ishii, T., Tateno, M., Ukai, W., Saito, S., Saito, T
Organizer
The 11th Congress of the European Society for Biomedical Research on Alcoholism
Place of Presentation
Berlin, Germany
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ethanol-induced neuronal damage and stem cell implantation. < ; Symposium> ; Asian-Pacific-European-Symposium2007
Author(s)
Tateno, M., Yoshinaga, T., Ishii, T., Ukai, W., Hashimoto, E., Saito, T
Organizer
The 11th Congress of the European Society for Biomedical Research on Alcoholism
Place of Presentation
Berlin, Germany
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The effects of antidepressants on the regulation of neuronal phenotype specific differentiation and platelet cytokines release in vivo2007
Author(s)
Ukai, W., Hashimoto, E., Watanabe, K., Imai, T., Ishii, T., Yoshinaga, T., Ono, T., Tateno, M., Saito, S., Saito, T
Organizer
The 37th annual meeting of the Society for Neuroscience
Place of Presentation
San Diego, U.S.A.
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The role of endoplasmic reticulum in the ethanol-induced neural stem cell dysfunction2007
Author(s)
Ishii, T., Ukai, W., Tateno, M., Yoshinaga, T., Ono, T., Watanabe, K., Saito, S., Hashimoto, E., Saito, T
Organizer
The 37th annual meeting of the Society for Neuroscience
Place of Presentation
San Diego, U.S.A.
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The effects of antidepressants on the phenotype specific neuronal differentiation in vitro2006
Author(s)
Ukai, W., Imai, T., Ishii, T., Kurosawa, S., Yoshinaga, T., Ono, T., Saito, S., Hashimoto, E., Ikeda, H., Saito, T
Organizer
Serotonin club 6th IUPHAR satellite meeting on serotonin
Place of Presentation
Sapporo, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The possible common pathophysiology of alcoholism and depression. < ; Symposium> ; 'A focus on Asia' -Alcohol and depression2006
Author(s)
Hashimoto, E., Ukai, W., Saito, S., Ikeda, H., Saito, T
Organizer
The 13th Congress of the International Society for Biomedical Research on Alcoholism
Place of Presentation
Sydney, Australia
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Molecular mechanism of neural network impairment : the possible common pathophysiology of alcoholism and depression. < ; Symposium> ; Role of glial cells in the development of dependence on drugs of abuse2006
Author(s)
Ukai, W., Saito, T., Ishii, T., Imai, T., Yoshinaga, T., Tateno, M., Saito, S., Hashimoto, E., Sohma, H
Organizer
The 13th Congress of the International Society for Biomedical Research on Alcoholism
Place of Presentation
Sydney, Australia
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Impairment of neural differentiation : the common mechanism of alcoholism and depression2006
Author(s)
Ishii, T., Ukai, W., Imai, T., Kurosawa, S., Yoshinaga, T., Tateno, M., Hashimoto, E., Saito, T
Organizer
The 13th Congress of the International Society for Biomedical Research on Alcoholism
Place of Presentation
Sydney, Australia
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of psychotropic drugs on neurogenesis and cytokine signaling. <BP Symposium>2006
Author(s)
Hashimoto, E., Ukai, W., Imai, T., Ishii, T., Kurosawa, S., Yoshinaga, T., Saito, S., Ikeda, H., Saito, T
Organizer
Joint Meeting of the 28th Annual Meeting of Japanese Society of Biological Psychiatry, the 36th Annual Meeting of Japanese Society of Neuropsychopharmacology and the 49th Annual Meeting of-the Japanese Society for Neurochemistry
Place of Presentation
Nagoya, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Neural stem cell transplantation for psychiatric disease using alcohol exposure model. <Workshop>2006
Author(s)
Yoshinaga, T., Ukai, W., Ishii, T., Imai, T., Kurosawa, S., Ono, T., Saito, S., Hashimoto, E., Ikeda, H., Saito, T
Organizer
Joint Meeting of the 28th Annual Meeting of Japanese Society of Biological Psychiatry, the 36th Annual Meeting of Japanese Society of Neuropsychopharmacology and the 49th Annual Meeting of the Japanese Society for Neurochemistry
Place of Presentation
Nagoya, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Analysis of antidepressants-induced neurogenesis by characterizin the neuronal phenotypes2006
Author(s)
Imai, T., Ukai, W., Ishii, T., Kurosawa, S., Yoshinaga, T., Ono, T., Saito, S., Hashimoto, E., Ikeda, H., Saito, T
Organizer
Joint Meeting of the 28th Annual Meeting of Japanese Society of Biological Psychiatry, the 36th Annual Meeting of Japanese Society of Neuropsychophannacology and the 49th Annual Meeting of the Japanese Society for Neurochemistry
Place of Presentation
Nagoya, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of SNC80 on hyper-emotional behavior of olfactory bulbectomized mice in the hole-board test2006
Author(s)
Oka, Y., Saitoh, A., Yamada, M., Yamada, M., Takahashi, T., Hirose, N., Kamei, J
Organizer
Joint Meeting of the 28th Annual Meeting of Japanese Society of Biological Psychiatry, the 36th Annual Meeting of Japanese Society of Neuropsychopharmacology and the 49th Annual Meeting of the Japanese Society for Neurochernistry
Place of Presentation
Nagoya, Japan
Description
「研究成果報告書概要(欧文)」より
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[Book] SSRIのすべて2007
Author(s)
橋本 恵理, 他
Publisher
先端医学社
Description
「研究成果報告書概要(和文)」より
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