title: Increased expression of ferritin, an iron-storage protein, in specific regions of the parahippocampal cortex of epileptic rats.
abstract: OBJECTIVE
  Iron accumulation in the brain has been associated with neurodegenerative disorders, including epilepsy. In our previous SAGE study, we showed that ferritin, an iron-storage protein, was one of the genes (Ferritin-H) that showed overexpression before the chronic epileptic phase. In this study we used ferritin as indicator for disturbed iron homeostasis to acquire insight into whether this could play a role in the pathogenesis of temporal lobe epilepsy.
  
  
  METHODS
  With immunocytochemistry, we studied the regional and cellular distribution of ferritin protein in an animal model for temporal lobe epilepsy in which spontaneous seizures develop a few weeks after electrically induced status epilepticus (SE).
  
  
  RESULTS
  Increased ferritin expression was observed in regions known to be vulnerable to cell death, mainly in reactive microglial cells of epileptic rats. Ferritin expression after SE was initially high, especially throughout the hippocampus, but decreased over time. In the chronic epileptic phase, it was still upregulated in regions where extensive cell loss occurs during the early acute and latent period. Within the parahippocampal region, the most persistent ferritin overexpression was present in microglial cells in layer III of the medial entorhinal area. The upregulation was most extensive in rats that had developed a progressive form of epilepsy with frequent seizures (approximately five to 10 seizures per day).
  
  
  CONCLUSIONS
  The fact that ferritin upregulation is still present in specific limbic regions in chronic epileptic rats, when neuronal loss is absent or minimal, suggests a role of iron in the pathogenesis and progression of epilepsy.
authors.affiliation: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands. gorter@science.uva.nl
authors.forename: Jan A
authors.initials: JA
authors.lastname: Gorter
authors.forename: Ana R M
authors.initials: AR
authors.lastname: Mesquita
authors.forename: Erwin A
authors.initials: EA
authors.lastname: van Vliet
authors.forename: Fernando H Lopes
authors.initials: FH
authors.lastname: da Silva
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000378:metabolism*; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020534:Parahippocampal Gyrus / Q000378:metabolism*; D051381:Rats; D013226:Status Epilepticus / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation
chemical_list: D005293:Ferritins