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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1588-1604
Number of pages17
JournalJournal of Neuroscience
Volume39
Issue number9
DOIs
Publication statusPublished - 27-02-2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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