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 language | English |
|---|---|
| Pages (from-to) | 1588-1604 |
| Number of pages | 17 |
| Journal | Journal of Neuroscience |
| Volume | 39 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 27-02-2019 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
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Acquired expression of mutant mitofusin 2 causes progressive neurodegeneration and abnormal behavior. / Ishikawa, Kaori; Yamamoto, Satoshi; Hattori, Satoko; Nishimura, Naoya; Tani, Haruna; Mito, Takayuki; Matsumoto, Hirokazu; Miyakawa, Tsuyoshi; Nakada, Kazuto.
In: Journal of Neuroscience, Vol. 39, No. 9, 27.02.2019, p. 1588-1604.Research output: Contribution to journal › Article
TY - JOUR
T1 - Acquired expression of mutant mitofusin 2 causes progressive neurodegeneration and abnormal behavior
AU - Ishikawa, Kaori
AU - Yamamoto, Satoshi
AU - Hattori, Satoko
AU - Nishimura, Naoya
AU - Tani, Haruna
AU - Mito, Takayuki
AU - Matsumoto, Hirokazu
AU - Miyakawa, Tsuyoshi
AU - Nakada, Kazuto
PY - 2019/2/27
Y1 - 2019/2/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062283517&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062283517&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2139-18.2018
DO - 10.1523/JNEUROSCI.2139-18.2018
M3 - Article
C2 - 30606759
AN - SCOPUS:85062283517
VL - 39
SP - 1588
EP - 1604
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 9
ER -