Protective effect of a prosaposin-derived, 18-mer peptide on slowly progressive neuronal degeneration after brief ischemia

Fumio Morita, Tong Chun Wen, Junya Tanaka, Ryuji Hata, Junzo Desaki, Kohji Sato, Kimihiko Nakata, Yong Jie Ma, Masahiro Sakanaka

研究成果: Article査読

18 被引用数 (Scopus)

抄録

Slowly progressive degeneration of the hippocampal CA1 neurons was induced by 3-minute transient global ischemia in gerbils. Sustained degeneration of hippocampal CA1 neurons was evident 1 month after ischemia. To investigate the effects of an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain (18MP) on this sustained neuronal degeneration, an intracerebroventricular 18MP infusion was initiated 3 days after ischemia. Histopathologic and behavior evaluations were conducted 1 week and 1 month after induction of ischemia. When compared with the vehicle infusion, 18MP treatment significantly increased the response latency time in a passive avoidance task. Increased neuronal density was also evident, as was the number of intact synapses in the hippocampal CA1 region at 1 week and 1 month after ischemia. 18MP treatment also significantly decreased the number of TUNEL-positive CA1 neurons 1 week after ischemia. Subsequent in vitro experiments using cultured neurons demonstrated that the 18MP at optimal extracellular concentrations of 1 to 100 fg/mL prevented nitric oxideinduced neuronal damage as expected and significantly upregulated the expressions of bcl-xL mRNA and its translated protein. These results suggest that the gerbil model of 3-minute ischemia is useful in studying the pathogenesis of slowly progressive neuronal degeneration after stroke and in evaluating effects of novel therapeutic agents. It is likely that the 18MP at low extracellular concentrations prevents neuronal apoptosis possibly through up-regulation of the mitochondrial antiapoptotic factor Bcl-xL.

本文言語English
ページ(範囲)1295-1302
ページ数8
ジャーナルJournal of Cerebral Blood Flow and Metabolism
21
11
DOI
出版ステータスPublished - 2001
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学

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