Neuronal degeneration and cognitive impairment can be prevented via the normalization of mitochondrial dynamics

Kaori Ishikawa, Satoshi Yamamoto, Satoko Hattori, Naoya Nishimura, Hirokazu Matsumoto, Tsuyoshi Miyakawa, Kazuto Nakada

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Neuronal cells possess a certain degree of plasticity to recover from cell damage. When the stress levels are higher than their plasticity capabilities, neuronal degeneration is triggered. However, the factors correlated to the plasticity capabilities need to be investigated. In this study, we generated a novel mouse model that able to express in an inducible manner a dominant-negative form of MFN2, a mitochondrial fusion factor. We then compared the phenotype of the mice continuously expressing the mutated MFN2 with that of the mice only transiently expressing it. Remarkably, the phenotypes of the group transiently expressing mutant MFN2 could be divided into 3 types: equivalent to what was observed in the continuous expression group, intermediate between the continuous expression group and the control group, and equivalent to the control group. In particular, in the continuous expression group, we observed remarkable hyperactivity and marked cognitive impairments, which were not seen, or were very mild in the transient expression group. These results indicate that abnormal mitochondrial dynamics lead to stress, triggering neuron degeneration; therefore, the neurodegeneration progression can be prevented via the normalization of the mitochondrial dynamics. Since the availability of mouse models suitable for the reproduction of both neurodegeneration and recovery at least partially is very limited, our mouse model can be a useful tool to investigate neuronal plasticity mechanisms and neurodegeneration.

Original languageEnglish
Article number105246
JournalPharmacological Research
Volume163
DOIs
Publication statusPublished - 01-2021

All Science Journal Classification (ASJC) codes

  • Pharmacology

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