A Novel Microfluidic Device-Based Neurite Outgrowth Inhibition Assay Reveals the Neurite Outgrowth-Promoting Activity of Tropomyosin Tpm3.1 in Hippocampal Neurons

Cell Mol Neurobiol. 2018 Nov;38(8):1557-1563. doi: 10.1007/s10571-018-0620-7. Epub 2018 Sep 14.

Abstract

Overcoming neurite inhibition is integral for restoring neuronal connectivity after CNS injury. Actin dynamics are critical for neurite growth cone formation and extension. The tropomyosin family of proteins is a regarded as master regulator of actin dynamics. This study investigates tropomyosin isoform 3.1 (Tpm3.1) as a potential candidate for overcoming an inhibitory substrate, as it is known to influence neurite branching and outgrowth. We designed a microfluidic device that enables neurons to be grown adjacent to an inhibitory substrate, Nogo-66. Results show that neurons, overexpressing hTpm3.1, have an increased propensity to overcome Nogo-66 inhibition. We propose Tpm3.1 as a potential target for promoting neurite growth in an inhibitory environment in the central nervous system.

Keywords: Microfluidic systems; Neurite outgrowth inhibition; NogoA; Tropomyosins.

MeSH terms

  • Animals
  • Hippocampus / cytology*
  • Humans
  • Lab-On-A-Chip Devices*
  • Neuronal Outgrowth* / drug effects
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nogo Proteins / pharmacology
  • Reproducibility of Results
  • Tropomyosin / metabolism*

Substances

  • Nogo Proteins
  • Tropomyosin