Induction of autophagy in neurite degeneration of mouse superior cervical ganglion neurons.
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.
Yang
Yi
Y
Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310027, P.R. China.
Fukui
Koji
K
Koike
Tatsuro
T
Zheng
Xiaoxiang
X
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D020932:Nerve Growth Factor / Q000378:metabolism; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology*; D013997:Time Factors; D014162:Transfection
D000590:Amino Acid Chloromethyl Ketones; D051017:Apoptosis Regulatory Proteins; C502661:Atg7 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D011506:Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C025946:3-methyladenine; D020932:Nerve Growth Factor; D000071193:Autophagy-Related Protein 7; D000225:Adenine