ERK1/2 activation in reactive astrocytes of mice with pilocarpine-induced status epilepticus

Neurol Res. 2009 Dec;31(10):1108-14. doi: 10.1179/174313209X389839. Epub 2009 Apr 28.

Abstract

Objective: To investigate the activation pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) in the hippocampus of mice during pilocarpine-induced status epilepticus (SE) and its relationship with reactive astrogliosis.

Methods: Status epilepticus (SE) models were established by intraperitoneal injection of pilocarpine. The intervention group received the ERK1/2 signaling pathway inhibitor SL327 before the pilocarpine injection. We evaluated the SE model group, the intervention group and the control saline-treated group, at 6 hours and 3 days after initiation of the seizure. Phosphorylated activated ERK1/2 and glial fibrillary acidic protein (GFAP) were labeled with both single-labeling and sequential single-labeling immunohistochemical techniques.

Results: Among the pilocarpine-treated (SE model) mice, strong immunohistochemical staining of phospho-ERK1/2 was observed in the neurons and astrocytes of the hippocampus at 6 hours after initiation of SE, whereas staining on the third day of SE was not different from the control saline-treated mice. In the SL327-treated mice (intervention group), SL327 effectively blocked the ERK1/2 activation and little gliosis could be detected at 6 hours and 3 days after initiation of SE; the levels of phospho-ERK1/2 remained low, but the level of gliosis was similar to that of SE mice.

Conclusion: The ERK1/2 signaling pathway plays an important role in the early stage of reactive astrogliosis in mice with pilocarpine-induced SE.

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Cell Count
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / metabolism*
  • Gliosis / pathology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Immunohistochemistry
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphorylation
  • Pilocarpine / pharmacology*
  • Random Allocation
  • Signal Transduction / physiology
  • Status Epilepticus / chemically induced
  • Status Epilepticus / metabolism*
  • Status Epilepticus / pathology
  • Time Factors

Substances

  • Glial Fibrillary Acidic Protein
  • Pilocarpine
  • Mitogen-Activated Protein Kinase 3