Regulation and role of ERK phosphorylation in glial cells following a nigrostriatal pathway injury

Brain Res. 2016 Oct 1;1648(Pt A):90-100. doi: 10.1016/j.brainres.2016.07.008. Epub 2016 Jul 8.

Abstract

This study was undertaken to examine the function of extracellular signal-regulated kinase (ERK) signaling pathway on the proliferation and activation of microglia/macrophage and astrocytes after brain injury in mice. The result of Western blot showed that p-ERK was immediately activated after injury (<4h), but the duration was short (<4 days). According to immunofluorescence double staining, it was found that at 4 and 8h after injury, p-ERK was expressed in microglia/macrophages, and that more cells were co-expressed by p-ERK and IBA-1 (microglia/macrophage marker) at 8h; at days 1 and 4, p-ERK was expressed in astrocytes, and more cells were co-expressed by p-ERK and GFAP (astrocyte marker) at day 4. After injury, the mice were injected with U0126 (MAPK/ERK signaling pathway inhibitor) via the femoral vein. Compared with those injected with DMSO, the cell number co-expressed by p-ERK and IBA-1 or GFAP significantly decreased (P<0.05). The increase of microglia/macrophage and astrocyte caused by injury was remitted, and the positive cell number significantly decreased (P<0.05). Western blot showed that the expression quantity of IBA-1 and GFAP significantly decreased (P<0.05). Furthermore, the ERK signaling pathway was involved in the proliferation and activation of the two glial cells types and improved long-term neurobehavioral function after brain injury. Therefore, the exploration of the formation mechanism of glial scar after injury and further research on the therapeutic method of neural regeneration are essential.

Keywords: Astrocyte; ERK signal pathway; Microglia/macrophage; Nigrostriatal pathway injury; U0126.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Blotting, Western
  • Brain Injuries / therapy
  • Butadienes / pharmacology
  • Butadienes / therapeutic use
  • Cell Proliferation / physiology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • MAP Kinase Signaling System / physiology*
  • Macrophages / metabolism
  • Male
  • Mice
  • Microglia / metabolism
  • Neuralgia / drug therapy
  • Neuroglia / metabolism*
  • Neuroglia / physiology
  • Nitriles / pharmacology
  • Nitriles / therapeutic use
  • Phosphorylation / physiology
  • Signal Transduction

Substances

  • Butadienes
  • Nitriles
  • U 0126
  • Extracellular Signal-Regulated MAP Kinases