title: Repeated PTZ treatment at 25-day intervals leads to a highly efficient accumulation of doublecortin in the dorsal hippocampus of rats.
abstract: BACKGROUND
  Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility.
  
  
  RESULTS
  By EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons.
  
  
  CONCLUSIONS
  Our results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy.
authors: Department of Psychiatry, Molecular Psychiatry, Rostock University Medical School, Rostock, Germany.
authors: Ana-Maria
authors: AM
authors: Buga
authors: Raluca
authors: R
authors: Vintilescu
authors: Adrian Tudor
authors: AT
authors: Balseanu
authors: Oltin Tiberiu
authors: OT
authors: Pop
authors: Costin
authors: C
authors: Streba
authors: Emil
authors: E
authors: Toescu
authors: Aurel
authors: A
authors: Popa-Wagner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D019070:Cell Lineage / Q000187:drug effects; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004334:Drug Administration Schedule; D004569:Electroencephalography; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007696:Kindling, Neurologic; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000008:administration & dosage* / Q000494:pharmacology*; D010641:Phenotype; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole