In vitro priming response in dorsal root ganglia partially mimics injury-driven pre-conditioning response and reprograms neurons for enhanced outgrowth

Mol Cell Neurosci. 2021 Jan:110:103573. doi: 10.1016/j.mcn.2020.103573. Epub 2020 Nov 25.

Abstract

Peripheral nerve injuries have the potential to bring about long-term disabilities in individuals. The major issue in repairing nerve injuries is the poor growth rate of axons. Although several molecules have been identified as potential candidates for improving axon growth, their potential translation into clinical practice is preliminary and largely unexplored. This necessitates identifying additional molecular candidates with superior potential to improve axon growth. Lack of a simple non-surgical screening model also poses a hurdle in rapidly screening potential candidate molecules. In this work, we developed a novel, rapid screening model for nerve regeneration therapeutics that retains a focus on adult neurons. The model involves simple incubation of sensory ganglia over a period of 24 h prior to dissociation. Surprisingly, this model features unique events that reprogram both sensory neurons and supporting glia favoring axon growth. Moreover, several associated cellular and molecular changes involved in this model partially mimic classic axotomy-induced changes in sensory ganglia. Overall, this model presents with a platform that not only allows rapid screening of drug candidates but offers opportunities in studying novel intrinsic molecular changes in both neurons and glial cells directed towards improving the pace of axon growth.

Keywords: DRG; In vitro priming; Nerve regeneration; Neurite outgrowth; Pre-conditioning response; Satellite glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / physiology
  • Cells, Cultured
  • Drug Discovery / methods*
  • Ganglia, Spinal / cytology
  • Male
  • Nerve Regeneration*
  • Neuroglia / drug effects
  • Neuronal Outgrowth*
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / physiology

Substances

  • Neuroprotective Agents

Grants and funding