Quantitative analysis of intraneuronal transport in human iPS neurons

J Pharmacol Sci. 2015 Aug;128(4):170-8. doi: 10.1016/j.jphs.2015.06.006. Epub 2015 Jun 27.

Abstract

Induced pluripotent stem (iPS) cells are promising tools to investigate disease mechanism and develop new drugs. Intraneuronal transport, which is fundamental for neuronal survival and function, is vulnerable to various pharmacological and chemical agents and is disrupted in some neurodegenerative disorders. We applied a quantification method for axonal transport by counting CM-DiI-labeled particles traveling along the neurite, which allowed us to monitor and quantitate, for the first time, intraneuronal transport in human neurons differentiated from iPS cells (iCell neurons). We evaluated the acute effects of several anti-neoplastic agents that have been previously shown to affect intraneuronal transport. Vincristine, paclitaxel and oxaliplatin decreased the number of moving particle along neurites. Cisplatin, however, produced no effect on intraneuronal transport, which is in contrast to our previous report indicating that it inhibits transport in chick dorsal root ganglion neurons. Our system may be a useful method for assessing intraneuronal transport and neurotoxicity in human iPS neurons.

Keywords: Anti-neoplastic agents; Intraneuronal vesicular transport; Neurotoxicity; Toxicity test; iPS cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Axonal Transport / drug effects
  • Axonal Transport / physiology*
  • Cells, Cultured
  • Chickens
  • Cisplatin / pharmacology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Neural Stem Cells / cytology*
  • Neurites / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Paclitaxel / pharmacology
  • Vincristine / pharmacology

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Vincristine
  • Paclitaxel
  • Cisplatin