Rho signaling inhibitor, CCG-1423, inhibits axonal elongation and dendritic complexity of rat cortical neurons

Biochem Biophys Res Commun. 2017 Oct 21;492(3):474-479. doi: 10.1016/j.bbrc.2017.08.071. Epub 2017 Aug 19.

Abstract

CCG-1423, a chemical inhibitor of Rho signaling, blocks serum response factor (SRF)/megakaryoblastic leukemia 1 (MKL1)-mediated gene expression by inhibiting the nuclear accumulation of MKL1. Several studies have suggested that CCG-1423 interacts not only with MKL1, which has a critical role in the regulation of neuronal morphology, but also with phosphatase and actin regulator 1 (Phactr1), which is localized at synapses. However, the effect of CCG-1423 on neuronal cells, especially on neuronal morphology, remains to be determined. In this study, we focused on the effect of CCG-1423 on axonal elongation, dendritic length, dendritic complexity and dendritic spine morphology. Incubation of cortical neuron cultures with up to 10 μM CCG-1423 for 72 h did not significantly affect cell viability. CCG-1423 inhibited axonal elongation and blocked the increase of dendritic length and complexity, but did not affect dendritic spine morphology. Here, we demonstrated for the first time that CCG-1423 affects neurite elongation, except for dendritic spines, without affecting neuronal cell viability. This study provides a better understanding of the effects of CCG-1423 on neurons, which may be useful for the assessment of the potential clinical application of CCG-1423 and its derivatives.

Keywords: Axon; CCG-1423; Cell viability; Dendrite; Dendritic spine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology*
  • Animals
  • Axons / drug effects*
  • Benzamides / pharmacology*
  • Cell Survival / drug effects
  • Cerebral Cortex / cytology*
  • Dendrites / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Neurons / cytology
  • Neurons / drug effects*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Anilides
  • Benzamides
  • CCG 1423