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Induction of autophagy in neurite degeneration of mouse superior cervical ganglion neurons

Authors

  • Yi Yang,

    1. Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310027, P.R. China
    2. Molecular Neurobiology Laboratory, Division of Life Science, Graduate School of Life Science, Hokkaido University, North Ward N10 W8, Sapporo 060-0810, Japan
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  • Koji Fukui,

    1. Molecular Neurobiology Laboratory, Division of Life Science, Graduate School of Life Science, Hokkaido University, North Ward N10 W8, Sapporo 060-0810, Japan
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  • Tatsuro Koike,

    1. Molecular Neurobiology Laboratory, Division of Life Science, Graduate School of Life Science, Hokkaido University, North Ward N10 W8, Sapporo 060-0810, Japan
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  • Xiaoxiang Zheng

    1. Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310027, P.R. China
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Dr Xiaoxiang Zheng, as above.
E-mail: zxx@mail.bme.zju.edu.cn
Dr Tatsuro Koike, as above.
E-mail: koike@sci.hokudai.ac.jp

Abstract

Emerging lines of evidence show that the mechanisms of neurite degeneration are convergent, with poor neuritic transport, mitochondrial dysfunction and an increase in intra-axonal calcium being the principal convergence points. Nevertheless, the details are unclear. Here, we revealed the induction of autophagy in degenerating neurites of sympathetic neuron initiated by three different experimental paradigms. Autophagosomes were colocalized with collapsed cytoskeletal proteins in neuritic beadings during degeneration. Accumulation of microtubule-associated protein light chain 3-II, which is the most reliable marker for autophagy, was observed in the early stage of neurite degeneration. The autophagy inhibitor 3-methyladenine efficiently suppressed neurite degeneration by protecting neurites from the loss of viability and mitochondrial function. Furthermore, knocking down the key autophagy-related genes Atg7 and Beclin1 significantly delayed axonal and dendritic degeneration after nerve growth factor deprivation. Reduced expression of Atg7 also suppressed neurite fragmentation after transection. Therefore, our present data suggest the critical role of autophagy in neurite degeneration and may provide a valuable clue in understanding the mechanism of axonal and dendritic degeneration.

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