2002 Fiscal Year Final Research Report Summary
A study on the molecular pathomechanisms underflying intractable epilepsy
| Project/Area Number |
12470287
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
TAKAHASHI Hitoshi NIIGATA UNIVERSITY Brain Research Institute, Professor, 脳研究所, 教授 (90206839)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Ryuichi NIIGATA UNIVERSITY Brain Research Institute, Professor, 脳研究所, 教授 (30018816)
NAWA Hiroyuki NIIGATA UNIVERSITY Brain Research Institute, Professor, 脳研究所, 教授 (50183083)
KAKITA Akiyoshi NIIGATA UNIVERSITY Brain Research Institute, Associate professor, 脳研究所, 助教授 (80281012)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Intractable epilepsy / Neuropathology / Molecular pathology / Gene analysis / DNA array / Brain developmental error / Cortical dysplasia / Neurosurgery for epilepsy |
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| Research Abstract |
1. We carried out the histopathological observations in 125 patients with pharmacoresistant intractable epilepsy. Cortical dysplasia (Grade I) in the medial temporal lobe was found to be the most frequent abnormality (66 cases). The mean ages at onset of seizure and at surgery were 12.2 years and 31.4 years, respectively. In all the cases, glial fibrillary acidic protein-positive reactive astrocytes were present in the affected cortex as well as in the subcortical white matter. The hippocampus was examined in a total of 32 cases : there were no correlation between histological severity of hippocampal sclerosis and that of cortical dysplasia.
2. We reported the histopathological features of an autopsy case of bilateral periventricular nodular heterotopia with widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex, in whom we found a novel exon 11 (Val528Met) filamin 1 mutation.
3. We employed the DNA array technique to compare the mRNA expression profiles of three neocortical subregions of the human brain : prefrontal cortex (Area 46), motor cortex (Area 4) and visual cortex (Area 17). The macroarray analysis on high quality mRNA from postmortem brains revealed that the expression profiles of the different cortical areas are almost similar : only six out of 1088 known genes exhibited significant differences (>2-fold) in their expression. RT-PCR studies with an increased number of samples confirmed that expression of only two genes, annexin II and early growth response protein 1, varied by 2-fold among the regions, whereas exoression of the others showed large inter-individual difference. These results suggest that the whole neocortex of humans is more homogeneous than we expected at the level of gross gene expression profiles.
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