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演題詳細

Poster

成体ラット運動ニューロン変性モデル脊髄における潜在的再生能
Latent neurogenic potential in adult rat spinal cord with motor neuron degeneration

  • P1-317
  • 割田 仁 / Hitoshi Warita:1 四條 友望 / Tomomi Shijo:1 池田 謙輔 / Kensuke Ikeda:1 小野 洋也 / Hiroya Ono:1 加藤 昌昭 / Masaaki Kato:1 鈴木 直輝 / Naoki Suzuki:1 船越 洋 / Hiroshi Funakoshi:2 青木 正志 / Masashi Aoki:1 
  • 1:東北大院医神経内科 / Dept Neurol, Univ of Tohoku, Sendai, Japan 2:旭川医大教育研究推進センター / Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa, Japan 

Amyotrophic lateral sclerosis (ALS) is an adult-onset devastating disease characterized by loss of motor neurons. Previous reports have shown adult neural stem/progenitor cells (NSPCs) reside within the ependymal layer of central canal throughout spinal cord in rodents. Although most of these NSPCs are dormant, they show multipotency under cultured condition. Moreover, acute injury induces proliferation and differentiation mainly leading to gliosis in vivo. The possible neurogenic niche in ALS-like chronic motor neuron degeneration, however, remains controversial. Here, we focused on the proliferating cells and microenvironment around the central canal in an ALS model.
We examined newly-generated cells and components of extracellular matrix such as chondroitin sulfate proteoglycans (CSPGs) in lumbar spinal cord cryosections of ALS-linked mutant SOD1 transgenic (Tg) rats at pre-, early, and late symptomatic stages with their age-matched non-transgenic (non-Tg) littermates. Newborn cells were labeled with a thymidine analogue. Under confocal laser scanning microscopy, multiple immunofluorescence using cell-selective markers revealed the cellular phenotypes. Based on the results, growth factors or vehicle was infused intrathecally in early symptomatic Tg rats for 14 days. Furthermore, we compared neuropathology between the treated and non-treated animals.
In contrast to non-Tg rats, the Tg rats showed a significant increase of newborn cells around the central canal. The proliferative cells contain glial cells, glial progenitors, ependymal cells, vascular endothelial cells, and undifferentiated neural progenitors. The growth factors-treated Tg rats showed a modest neuroprotection against the ALS-like disease with increased proliferation of undifferentiated progenitors, but decreased glial proliferation around the central canal. Concomitantly, deposition of the gliosis-related CSPGs was diminished in the treated rats.
The present results have shown neurodegeneration-induced endogenous regenerative response in the adult spinal cord, suggesting a possible target for regenerative therapy in ALS.

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