Acquired expression of mutant mitofusin 2 causes progressive neurodegeneration and abnormal behavior

Kaori Ishikawa, Satoshi Yamamoto, Satoko Hattori, Naoya Nishimura, Haruna Tani, Takayuki Mito, Hirokazu Matsumoto, Tsuyoshi Miyakawa, Kazuto Nakada

研究成果: Article

抜粋

Neurons have high plasticity in developmental and juvenile stages that decreases in adulthood. Mitochondrial dynamics are highly important in neurons to maintain normal function. To compare dependency on mitochondrial dynamics in juvenile and adult stages, we generated a mouse model capable of selective timing of the expression of a mutant of the mitochondrial fusion factor Mitofusin 2 (MFN2). Mutant expression in the juvenile stage had lethal effects. Contrastingly, abnormalities did not manifest until 150 d after mutant expression during adulthood. After this silent 150 d period, progressive neurodegeneration, abnormal behaviors, and learning and memory deficits similar to those seen in human neurodegenerative diseases were observed. This indicates that abnormal neuronal mitochondrial dynamics seriously affect survival during early life stages and can also significantly damage brain function after maturation. Our findings highlight the need to consider the timing of disease onset in mimicking human neurodegenerative diseases.

元の言語English
ページ(範囲)1588-1604
ページ数17
ジャーナルJournal of Neuroscience
39
発行部数9
DOI
出版物ステータスPublished - 27-02-2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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