| Project/Area Number |
17591129
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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 | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
HAYASHI Masaharu Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Organization for Medical Research Tokyo Metropolitan Institute for Neuroscience, Director (00280777)
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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 |
¥3,670,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | progressive myoclonus epilepsy / DRPLA / West syndrome / Lennox-Gastaut syndrome / oxidative stress / immunohistochemistry / ELISA / intractable epilepsy / Lennox Gastaut症候群 / Hexanoyl lysine / 低血糖発作 / Focal cortical dysplasia / 片側巨脳症 / 8-Hydroxy-2'-deoxyguanosine / 4-Hydroxynonenal / 福山型先天性筋ジストロフィー / 大脳白質信号異常 / 歯状核赤核淡蒼球ルイ体萎縮症 / 酸化的障害 / 淡蒼球 / 8-hydroxy-2'-deoxyguanosine / Superoxide dismutase |
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| Research Abstract |
Dentatorubral-pallidoluysian atrophy (DRPLA) is classified into juvenile and early adult types showing progressive myoclonus epilepsy (PME) in addition to late adult type. We immunohistochemically examined accumulation of oxidative products and expression of superoxide dismutase (SOD) in autopsy cases of DRPLA. Oxidative products to DNA (8-OHdG) were accumulated in the lenticulate nucleus predominantly in DRPLA cases having PME. Cytoplasmic immunoreactivity for Cu/ZnSOD was reduced in the external segment of globus pallidus, dentate nucleus and cerebellar cortex in DRPLA cases. Mitochondrial immunoreactivity for MnSOD was reduced in the lenticulate nucleus and cerebellum in DRPLA cases having PME It is likely that oxidative stress can be involved in DRPLA.
West syndrome (WS) consists of epileptic spasms, developmental delay, and hypsarrhythmia on EEG. We immunohistochemically examined accumulation of oxidative products and SOD expression in the brains of 4 autopsy cases each with lissencephaly and perinatal hypoxemic ischemic encephalopathy (HIE), and suffering from both WS and Lennox-Gastaut syndrome (LGS). In the absence of destructive changes, 3 of 4 lissencephaly cases and 2 of 4 HIE cases showed neurons immunoreactive for oxidative stress marker to lipids in the midbrain in the WS/LGS autopsy cases. Immunoreactivities for SODs were well preserved in the brain area including the midbrain. We also measured the levels of oxidative stress marker, 8-OHdG and markers for lipid peroxidation such as hexanoyl-lysine adduct (HEL) in the urine and cerebral spinal fluid (CSF) of 11 WS patients using ELISA. In the CSF, 8-OHdG level was increased in 3 of 4 patients in the symptomatic group. HEL level in the CSF was increased in 2 of 7 patients in the cryptogenic group, and in 2 of 4 patients in the symptomatic group. Lipid peroxidation is likely to be involved in the persistence of epileptic seizures in patients with WS.
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