1999 Fiscal Year Final Research Report Summary
On the mechanism of cerebellar foliation and its abnormal development
| Project/Area Number |
09680741
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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 | Nagoya University |
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Principal Investigator |
INOUYE Minoru Nagoya Univ., Res. Inst. Environ. Med., Associate Professor, 環境医学研究所, 助教授 (20090425)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGISHI Yoshiko Nagoya Univ., Res. Inst. Environ. Med., Research Associate, 環境医学研究所, 助手 (50024659)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Cerebellum / extracellular matrix / foliation / prenatal exposure / Purkinje cell / radiation / rat / Reelin |
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| Research Abstract |
Prenatal X-irradiation of rats during the late gestation period induces ectopic Purkinje cells in abnormally foliated cerebellum. To examine mechanisms of abnormal migration of Purkinje cells by X-radiation, pregnant rats were exposed to 2.5 Gy X-radiation on gestation day 21, and the cerebellum of progeny was examined using immunohistochemistry for identification of Purkinje and Bergmann cells. Six hours after exposure, extensive cell death was observed in the external granular layer (EGL). By postnatal day (P) 9, while Purkinje cells with well developed dendrites were aligned underneath the EGL in the control cerebellum, Purkinje cells with shorter and abnormally oriented dendrites failed to align and remained in the ectopic location mainly in the internal granular layer (IGL), and abnormal folia developed in the irradiated rats. Expression of cell adhesion molecules, i.e., neural cell adhesion molecule (NCAM), fibronectin, tenascin and Reelin, was examined by immunochemistry. Among them the expression of Reelin was affected most prominently. Reelin expression strikingly decreased in the premigratory zone of EGL and IGL in the irradiated cerebellum on P1, and the decrease continued until P9. Northern blot analysis also revealed significant decrease in Reelin mRNA by irradiation from P0, being almost one third of level in controls. The decrease continued up to P9. Expressions of other cell adhesion molecules examined were not affected following exposure and around the Purkinje cells. The results demonstrated that X-radiation caused disruption of EGL and reduced secretion of Reelin. Since Reelin has been shown to play important roles in the migration of neural cells, it is suggested that the decrease in Reelin is an important factor in the disturbed migration of Purkinje cells. The derangement of Purkinje cells may result in the abnormal foliation of the cerebellum by X-irradiation.
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