First published March 1, 2017 - More info
Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies.
Sergio Gonzalez, Jade Berthelot, Jennifer Jiner, Claire Perrin-Tricaud, Ruani Fernando, Roman Chrast, Guy Lenaers, Nicolas Tricaud
Original citation: J Clin Invest. 2016;126(3):1023–1038. https://doi.org/10.1172/JCI84505
Citation for this retraction: J Clin Invest. 2017;127(3):1115. https://doi.org/10.1172/JCI92100
Following an institutional investigative review of multiple errors in data presentation in this paper, including several instances of reuse of the same images to represent independent samples in Supplemental Figures 7 and 11, the Editorial Board is retracting this paper. The institutional review found no evidence of intention to falsify results and concluded that errors were made due to negligence during the assembly of figures. The institutional review panel did not question in any way the authenticity of the published results. The paper is being retracted because JCI editorial policy prohibits image duplication and misrepresentation of data.
See the related article at Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies.