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

Yi Yang, Koji Fukui, Tatsuro Koike, Xiaoxiang Zheng

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91 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2979-2988
Number of pages10
JournalEuropean Journal of Neuroscience
Volume26
Issue number10
DOIs
Publication statusPublished - 2007 Nov
Externally publishedYes

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Keywords

  • 3-methyladenine
  • Beading
  • Microtubule-associated protein light chain 3
  • Nerve growth factor deprivation
  • RNA interference

ASJC Scopus subject areas

  • Neuroscience(all)

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