2007 Fiscal Year Final Research Report Summary
Neuropathological and therapeutic studies on adult motoneuron degeneration using rat peripheral nerve avulsion models
| Project/Area Number |
17590908
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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 |
Neurology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
WATABE Kazuhiko Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Senior Scientist (30240477)
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| Co-Investigator(Kenkyū-buntansha) |
OYANAGI Kiyomitsu Tokyo Metropolitan Organization for Medical Research, Senior Scientist (00134958)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Adenovirus vector / Avulsion / Facial nerve / Motoneuron / ALS / neural progenitor |
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| Research Abstract |
Neurogenesis occurs throughout life in two specific regions of the adult mammalian brain; the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. After injury and pathological stimulations, adult neurogenesis has also been demonstrated in regions otherwise considered to be non-neurogenic. We investigated proliferation of nestin-immunoreactive (IR) neural progenitor cells (NPCs) in injured facial nuclei after facial nerve avulsion in adult rats. The facial nerve of 3 month-old Fischer 344 male rats was either avulsed or distally axotomized, and facial nuclei were histologically examined at different time points. Two weeks after avulsion, motoneuron death becomes apparent and nestin-IR cells proliferated in lesioned facial nuclei. Neither motoneuron death nor proliferation of nestin-IR cells was evident in facial nuclei after distal axotomy. When intact facial nuclei were dissociated and cultured in the presence of fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF), neurospheres formed and nestin-IR NPCs could be expanded and passaged for over 8 months. In vitro proliferation of NPCs derived from avulsed facial nuclei was much more vigorous than that from intact nuclei. These NPCs differentiated to neurons, astrocytes, and oligodendrocytes in the presence of all trans retinoic acid. In vivo local treatment of an adenoviral vector encoding FGF2 after avulsion significantly increased nestin-IR cells in lesioned facial nuclei. These results indicate that adult rat facial nerve avulsion model is a novel tool to investigate endogenous NPCs in adult rat brain, and could be used to screen candidate therapeutics to promote in vitro and in vivo neurogenesis against neurodegenerative disorders.
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