The study of neurodegeneration as a prognostic factor in congenital dysplasia of cortical white matter

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19679
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Li Heng 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第二部, 科研費研究員 (70621994)
• Research Collaborator: Inoue Ken
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 先天性大脳白質形成不全 / 神経変性

Outline of Final Research Achievements

Pelizaeus-Merzbacher (PMD) disease is a representative disease of congenital hypomyelinating leukodystrophies of the central nervous system (CNS). Common clinical features of PMD patients can be recognized as hypotonia, nystagmus and delay in developmental milestones within the first year of life. However, the motor functions of the PMD patients always decline slowly after 10 years of age. As a cause of this late-oneset motor dysfunction, it is considered that dysmyelination causes neurodegeneration following aberrant axonal energy metabolism. We confirmed the pathological appearances of axonal degeneration and abnormal of neurotransmission via morphological, electrophysiological, and molecular biological studies in PMD model mice. Elucidating the mechanism of the neurodegeneration may serve as a basis for prevention of the secondary neurological symptoms in the future treatment of hypomyelinating leukodystrophies.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

学術的及び社会的意義は、①これまで検証されていないPelizaeus-Merzbacher病の神経細胞体変性に対して、生理機能と病態表現の面で検証することができるということである。②髄鞘形成不全における神経細胞体変性のメカニズムを解明することにより、当疾患の二次的な症状の悪化の予防及び治療法開発のための基盤になる知見を得ることが出来る点である。③本研究の成果は、新しい治療法の評価手段としても応用できる。