| Project/Area Number |
23500438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
ENOKIDO Yasushi 愛知県心身障害者コロニー発達障害研究所, 病理学部, 室長 (90263326)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Takuya 東京医科歯科大学, 難治疾患研究所, 助教 (80396647)
KOUCHI Zen 愛知県心身障害者コロニー, 発達障害研究所, 研究員 (70322485)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | アストロサイト / ホモシステイン / 神経細胞死 / エピジェネティックス / グリア細胞 / ヒストンリン酸化 / エピゲノム制御 / 神経幹細胞 / 脳代謝 / 先天性代謝異常 / 発達障害 |
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| Outline of Final Research Achievements |
Cystathionine β-synthase (CBS) is a key enzyme in the generation of cysteine from methionine, and occupies a crucial regulatory position between the methionine cycle and transsulfuration pathway. CBS deficiency causes homocystinuria, an inborn error of homocysteine (Hcy) metabolism associated with neuro-psychological disorders, such as mental retardation, seizure and depression. In this study, we used CBS deficient mice (CBS-/- mouse) and examined their neuropathology. CBS-/- mice exhibited brain malformation and neuronal apoptosis from early postnatal age. Using an in vitro co-culture system, we showed that Hcy released from astrocytes causes oxidative stress and DNA damage, which result in non-cell autonomous neurotoxicity. Our results suggest that complementary Hcy metabolism between neuron and astrocyte plays a critical role for normal development and highly organized functions of the brain.
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