title: Monocyte chemoattractant protein-1 affects migration of hippocampal neural progenitors following status epilepticus in rats.
abstract: BACKGROUND
  Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. The mechanisms for epilepsy formation remain unknown. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. In the present study, we investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in aberrant migration of hippocampal progenitors in rats after the insult of status epilepticus (SE).
  
  
  METHODS
  SE was induced with pilocarpine in Sprague-Dawley rats. Transcriptional expression of MCP-1 in the dentate gyrus (DG) was measured using quantitative real-time PCR. From 1 to 28 days after SE, the temporal profiles of MCP-1 protein expression in DG were evaluated using enzyme-linked immunosorbent assay. Chemokine (C-C motif) receptor 2 (CCR2) expression in doublecortin-positive neuronal progenitors was examined using double-labeling immunohistochemistry. The involvement of MCP-1/CCR2 signaling in aberrant neuronal progenitor migration in the epileptic hippocampus was assessed in the SE rats using a CCR2 antagonist, RS102895, and the ectopic migration of neuronal progenitors was determined using Prox1/doublecortin double immunostaining.
  
  
  RESULTS
  After SE, MCP-1 gene was significantly upregulated and its corresponding protein expression in the DG was significantly increased on days 1 and 3. Some hilar ectopic progenitor cells of SE rats expressed the MCP-1 receptor, CCR2. Notably, the ectopic migration of neuronal progenitors into hilus was attenuated by a blockade of the MCP-1/CCR2 interaction with a selective CCR2 inhibitor, RS102895.
  
  
  CONCLUSIONS
  An increase in dentate MCP-1 is associated with seizure-induced aberrant migration of neuronal progenitors through the interaction with CCR2. The upregulation of MCP-1 after an insult of SE may play a role in the generation of epilepsy.
authors: Institute of Physiology, National Yang-Ming University, No,155, Sec, 2, Linong Street, Taipei, 112, Taiwan.
authors: Yu-Wen
authors: YW
authors: Hung
authors: Ming-Tsong
authors: MT
authors: Lai
authors: Yi-Jhan
authors: YJ
authors: Tseng
authors: Chien-Chen
authors: CC
authors: Chou
authors: Yung-Yang
authors: YY
authors: Lin
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein