Intermittent Fasting Alleviates the Neuropathic Phenotype in a Mouse Model of Charcot-Marie-Tooth Disease

Neurobiol Dis. 2009 Apr;34(1):146-54. doi: 10.1016/j.nbd.2009.01.002.

Abstract

Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Basement Membrane / physiopathology
  • Cell Proliferation
  • Charcot-Marie-Tooth Disease / diet therapy*
  • Charcot-Marie-Tooth Disease / pathology
  • Charcot-Marie-Tooth Disease / physiopathology
  • Disease Models, Animal
  • Fasting*
  • Locomotion
  • Male
  • Mice
  • Mice, Mutant Strains
  • Myelin Proteins / metabolism
  • Myelin Proteins / physiology
  • Myelin Sheath / physiology
  • Myelin Sheath / ultrastructure
  • Schwann Cells / physiology
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiopathology

Substances

  • Myelin Proteins
  • Pmp22 protein, mouse