Ibuprofen does not inhibit RhoA-mediated growth cone collapse of embryonic chicken retinal axons by LPA

Exp Brain Res. 2021 Oct;239(10):2969-2977. doi: 10.1007/s00221-021-06172-y. Epub 2021 Jul 28.

Abstract

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that causes neuronal growth cones to collapse and neurites to retract through a RhoA-ROCK mediated pathway. It has been reported that the NSAID ibuprofen improves regeneration after spinal cord injury through a mechanism of inhibiting RhoA. This leads to the hypothesis that ibuprofen should block LPA-mediated growth cone collapse. We tested this hypothesis by treating embryonic chick retinal neurons with ibuprofen followed by LPA. Retinal growth cones collapsed with LPA in the presence of ibuprofen similar to control; however, growth cone collapse was effectively blocked by a ROCK inhibitor. Thus, our results do not support the designation of ibuprofen as a direct RhoA inhibitor.

Keywords: Growth cone; Ibuprofen; Lysophosphatidic acid; Retinal ganglion cells; RhoA.

MeSH terms

  • Animals
  • Axons
  • Cells, Cultured
  • Chick Embryo
  • Chickens*
  • Growth Cones*
  • Ibuprofen / pharmacology
  • Lysophospholipids / pharmacology

Substances

  • Lysophospholipids
  • lysophosphatidic acid
  • Ibuprofen