Oxydative phosphorylation in sciatic nerve myelin and its impairment in a model of dysmyelinating peripheral neuropathy

J Neurochem. 2013 Jul;126(1):82-92. doi: 10.1111/jnc.12253. Epub 2013 Apr 30.

Abstract

Myelin sheath is the proteolipid membrane wrapping the axons of CNS and PNS. We have shown data suggesting that CNS myelin conducts oxidative phosphorylation (OXPHOS), challenging its role in limiting the axonal energy expenditure. Here, we focused on PNS myelin. Samples were: (i) isolated myelin vesicles (IMV) from sciatic nerves, (ii) mitochondria from primary Schwann cell cultures, and (iii) sciatic nerve sections, from wild type or Charcot-Marie-Tooth type 1A (CMT1A) rats. The latter used as a model of dys-demyelination. O₂ consumption and activity of OXPHOS proteins from wild type (Wt) or CMT1A sciatic nerves showed some differences. In particular, O₂ consumption by IMV from Wt and CMT1A 1-month-old rats was comparable, while it was severely impaired in IMV from adult affected animals. Mitochondria extracted from CMT1A Schwann cell did not show any dysfunction. Transmission electron microscopy studies demonstrated an increased mitochondrial density in dys-demyelinated axons, as to compensate for the loss of respiration by myelin. Confocal immunohistochemistry showed the expression of OXPHOS proteins in the myelin sheath, both in Wt and dys-demyelinated nerves. These revealed an abnormal morphology. Taken together these results support the idea that also PNS myelin conducts OXPHOS to sustain axonal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Adenosine Triphosphate / metabolism
  • Animals
  • Axons / metabolism
  • Blotting, Western
  • Cells, Cultured
  • Charcot-Marie-Tooth Disease / metabolism
  • Charcot-Marie-Tooth Disease / pathology
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / pathology
  • Immunohistochemistry
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Mitochondria / metabolism
  • Myelin Sheath / metabolism*
  • Myelin Sheath / ultrastructure
  • Oxidative Phosphorylation*
  • Oxygen Consumption / physiology
  • Peripheral Nervous System Diseases / metabolism*
  • Peripheral Nervous System Diseases / pathology
  • Proton-Translocating ATPases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Schwann Cells / metabolism
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiology*

Substances

  • Adenosine Triphosphate
  • Proton-Translocating ATPases