Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy

J Peripher Nerv Syst. 2017 Sep;22(3):162-171. doi: 10.1111/jns.12219.

Abstract

Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development.

Keywords: NMNAT2; Sarm1; Wallerian degeneration; Wlds; diabetic neuropathy; distal axon degeneration; paclitaxel; peripheral neuropathy.

Publication types

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

MeSH terms

  • Action Potentials / genetics
  • Analysis of Variance
  • Animals
  • Antineoplastic Agents, Phytogenic / toxicity
  • Armadillo Domain Proteins / deficiency*
  • Armadillo Domain Proteins / genetics
  • Cytoskeletal Proteins / deficiency*
  • Cytoskeletal Proteins / genetics
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Hyperalgesia / etiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Conduction / genetics
  • Paclitaxel / toxicity
  • Pain Threshold / physiology
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / prevention & control*
  • Reaction Time / genetics
  • Sural Nerve / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • Armadillo Domain Proteins
  • Cytoskeletal Proteins
  • SARM1 protein, mouse
  • Paclitaxel