Study of Neuropathology caused by defective amino acid metabolism in astrocyte lineage cells.

2014 Fiscal Year Final Research Report

• Project/Area Number: 23500438
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• 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)
• 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)
• Project Period (FY): 2011-04-28 – 2015-03-31
• 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

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.

Free Research Field

神経化学