2002 Fiscal Year Final Research Report Summary
Regional Specification and regeneration of the Mammalian Central Nervous System
| Project/Area Number |
12210004
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKAFUKU Masato The University of Tokyo, Graduate School of Medicine, associate professor, 大学院医学研究科, 助教授 (80202216)
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| Project Period (FY) |
2000 – 2002
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| Keywords | neural development / transcription factor / neural stem cell / neuron / regeneration / regional specification / neurological disease / stroke |
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| Research Abstract |
In adult tissues with high regenerative capacity, such as skin and liver, dead cells can be replaced either by the proliferation of nearby cells or resident stem cells. Unlike these cases, it has long been thought that the adult mammalian central nervous system (CNS) is incapable of significant self-repair or regeneration due to the lack of such sources for cell replacement. Many lines of studies in the past decade have revealed, however, that progenitors with the ability to produce new neurons and glia remain in the adult CNS. In particular, neural stem cells defined with the characteristics of long-term self-renewal and multi-lineage differentiation have been shown to persist throughout life in various mammalian species including humans. The adult CNS has also been shown to contain a range of progenitors with more limited capacities of growth and differentiation. Furthermore, these neural progenitors have been shown to continue neurogenesis in some regions of the adult brain. These new findings have raised the intriguing possibility that such endogenous cells may be recruited to repair the damaged CNS. In this study we demonstrated that activation of endogenous progenitors leads to massive regeneration of hippocampal pyramidal neurons after ischemia in rats. Endogenous progenitors proliferate in response to ischemia, and subsequently migrate into the hippocampus to regenerate new neurons.
Intraventricular infusion of growth factors markedly augments these responses, thereby increasing the number of newborn neurons. Our studies suggest that regenerated neurons are integrated into the existing brain circuitry, and contribute to ameliorating neurological deficits. These results expand the possibility of neuronal regeneration therapies for stroke and other neurological diseases.
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Research Products
(20 results)
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[Journal Article] Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor.2001
Author(s)
Yamamoto N, Yamamoto S, Inagaki F, Kawaichi M, Fukamizu A, Kishi N, Matsuno K, Nakamura K, Weinmaster G, Okano H, Nakafuku M.
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Journal Title
J.Biol.Chem. 276
Pages: 45031-45040
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord.2001
Author(s)
Yamamoto S, NagaoM, Sugimori M, Kosako H, Nakatomi H, Yamamoto N, Takebayashi H, Nabeshima Y, Kitamura T, Weinmaster G, Nakamura K, Nakafuku M.
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Journal Title
J.Neurosci. 21
Pages: 9814-9823
Description
「研究成果報告書概要(欧文)」より
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