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Adult Neurogenesis

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Selective vulnerability and dispersion of dentate granule cells and their progenitors in pilocarpine-induced status epilepticus rat model

  • P3-089
  • 上森 健至 / Takeshi Uemori:1 戸田 景子 / Keiko Toda:1 石 龍徳 / Tatsunori Seki:1 
  • 1:東京医科大学 / Department of Histology and Neuroanatomy, Tokyo Medical University 

Pilocarpine-induced status epilepticus model in rodents has been commonly used to study the mechanisms of human temporal epilepsy. The epileptic seizures not only causes abnormal cellular organization in the dentate gyrus, but also increases neurogenesis of dentate granule cells that is known to persists throughout life. Here we examined the structural changes including neurogenesis along the septo-temporal axis of the dentate gyrus in seizures-induced rats. Male rats were pretreated with atropin methylbromide and were administered pilocarpine hydrochloride to induce epileptic seizures. Three hours later epileptic seizures were terminated with diazepam. Ten days after the seizures animals were sacrificed, and their hippocampi were fixed in fixative containing 4% paraformaldehyde. Tissue sections of the hippocampus were immunostained with antibodies against NeuN, Prox1 and PSA-NCAM, and were observed using confocal laser microscope. In rats that displayed seizure activity, selective loss of prox1 and NeuN expressions was observed only in a part or whole of the suprapyramidal blade of dentate granule cell layer (GCL), although some positive cells remain in subgranular zone (SGZ). On the other hand, no change was found in the infrapyramidal blade. PSA-NCAM-expressing newly generated granule cells are found more in the infrapyramidal blade than in the suprapyramidal blade. In the Prox1-negative regions of the suprapyramidal blade, a few PSA+/Prox1+ presumptive immature granule cells with small nucleus were observed in SGZ, GCL and inner molecular layer. They appear to migrate from the SGZ to the molecular layer. The appearance resembles to granule cell dispersion in human temporal lobe epilepsy. Furthermore, the disappearance of Prox1 and NeuN expressions was remarkable at the middle part of sept-temporal axis in hippocampus, and was scarcely detected near temporal pole. The damaged area changed gradually along the septo-temporal axis. These results suggest that the granule cell layer has distinct subdivisions along the septo-temporal axis, and in infra- and suprapyramidal blades in terms of the vulnerability to epileptic seizures and seizure-induced neurogenesis.

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