| Project/Area Number |
16500234
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
KAWANO Hitoshi Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 東京都神経科学総合研究所, 副参事研究員 (20161341)
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| Co-Investigator(Kenkyū-buntansha) |
SANGO Kazunori Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 副参事研究員 (50291943)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | mouse / brain / neural regeneration / fibrotic scar / reactive astrocytes / chondroitin sulfate proteoglycan / type IV collagen / 損傷 / ドーパミンニューロン / IV型コラーゲン / 反応性アストロサイト |
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| Research Abstract |
To investigate the mechanism of the age-related failure of regeneration of transected axons, nigrostriatal dopaminergic axons were unilaterally transected in the lateral hypothalamus in adult mice and in immature mice aged postnatal days 7, 14 and 21. Ten days after the transection, tyrosine hydroxylase-immunoreactive axons had regenerated from caudal to rostral across the lesion site in mice transected at postnatal day 7, while they stopped and did not extend across the lesion site in mice transected at postnatal day 14 or older. Reactive astrocytes bearing chondroitin sulfate proteoglycans were observed around the lesion in mice transected at all ages. However, a fibrotic scar containing type IV collagen-immunoreactive deposits which was consistently formed at the lesion site in mice transected at postnatal day 14 or older, was not formed in mice lesioned at postnatal day 7. When 2,2'-dipyridyl, an inhibitor of collagen synthesis, was injected into the lesion site at the time of transection in both postnatal day 14 and adult mice, the deposition of type IV collagen and the formation of a fibrotic scar were completely prevented, and a large number of tyrosine hydroxylase-immunoreactive axons extended across the lesion and reinnervated the striatum. These results imply that the fibrotic scar formed in the lesion site is a crucial impediment to the regeneration of ascending dopaminergic axons in adult mice, and suggest that type IV collagen is required for the development of the fibrotic response to adult brain injury.
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