| Project/Area Number |
17591104
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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 |
Pediatrics
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| Research Institution | Ibaraki Prefectural University of Health Sciences |
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Principal Investigator |
IWASAKI Nobuaki Ibaraki Prefectural University of Health Sciences, 付属病院, Associate professor (70251006)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Akira Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Department of Neurosurgery, Professor (90241819)
NITTA Naotaka Ibaraki Prefectural University of Health Sciences, The National Institute of Advanced Industrial Science and Technology, Institute for Human Science & Biomedical Engineering, biomedical sensing and imaging group, Researcher (60392643)
NUMANO Shoichi Tokyo Metropolitan University, Department of Radiological Science, Graduate School of Human Health Science, Assistant Professor (10399511)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,740,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | myelination / dysmyelination / myelin basic protein / magnetic resonance imaging / diffusion weighted MRI / mutant mouse / shiverer mouse / 18q-syndrome / 磁気共鳴画像 / 拡散画像法 / 髄鞘形成 / MBP / 拡散画像 |
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| Research Abstract |
Diffusion-weighted magnetic resonance imaging techniques were developed with MRI equipment specifically designed for small experimental animals. The diffusion-weighted images using a three-dimensional MP-RAGE MRI sequence, in addition to the conventional multislice spin-echo sequence, were performed on rats. Subsequently, the diffusion-weighted images and apparent diffusion coefficient maps were acquired in which a new saddle coil was adjusted for use on the mouse brain.
The temporal order of the myelination of the nerve tracts was quantitatively analyzed using immunohistochemistry with anti-myelin basic protein (MBP) antibody, anti-proteolipid protein (PLP) antibody and anti-myelin associated glycoprotein (MAG) antibody. This analysis was performed on the brains of wild-type, heterozygous mutant (MBPshi/+) and homozygous mutant (MBPshi/MBPshi) shiverer mice. No difference in the staining intensities of MBP, PLP and MAG was revealed between the wild-types and heterozygous mutants. On th
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e other hand, in the homozygous shiverer mutant, decreases in staining intensities for MBP and PLP were apparent, although MAG staining intensity appeared similar to the level observed in wild-type and heterozygous mice. Therefore, it seemed necessary to analyze the relationship between MBP and MAG.
A boy afflicted with chromosome 18 ring was investigated by brain MRI and autopsy examination. The T2 weighted image revealed diffuse high intensity signals throughout the cerebral white matter. The cerebral white matter was clearly described in the immunohistochemical staining for MBP and PLP.Electron microscopy revealed clusters of axons wrapped by compact myelin sheaths with distinct major dense lines. Holzer staining and immunohistochemical staining for GFAP revealed gliosis of the cerebral white matter.
It has previously been assumed that the high intensity signal of T2 weighted MRI images was caused by dysmyelination resulting from MBP gene abnormality. However, our pathological study demonstrated that the gliosis of cerebral white matter was an important cause for MRI abnormality instead of dysmyelination. We show the importance of using pathophysiological analysis in combination with MRI imaging in evaluating this mutant mouse as a valid animal model. Less
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