Continuous administration of poloxamer 188 reduces overload-induced muscular atrophy in dysferlin-deficient SJL mice

Naoki Suzuki, Tetsuya Akiyama, Toshiaki Takahashi, Hazuki Komuro, Hitoshi Warita, Maki Tateyama, Yasuto Itoyama, Masashi Aoki

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Dysferlin-deficient SJL mice are commonly used to study dysferlinopathy. We demonstrated that poloxamer 188 (P188), a membrane sealant, is effective in reducing the loss of muscle mass in SJL mice when administered using an osmotic pump for 6 weeks. We did not observe significant changes over a 2-week administration period, suggesting that longthier observation is necessary to determine the effectiveness of P188. We also examined exercise endurance in P188-administered SJL mice using a rolling cage. Phosphorylated p38 was found to be reduced in P188-administered SJL mice; additionally, using microarray analysis, we found diminished expression of atrogin-1, an E3 ubiquitin ligase, as the effector of muscular atrophy. Chronic infusion of P188 to dysferlin-deficient SJL mice reduced muscular atrophy, and administering p38 and atrogin-1 in the gastrocnemius muscle improved its motor function. These results provide a basis for potential treatments for dysferlin-deficient skeletal muscle fibers.

Original languageEnglish
Pages (from-to)181-186
Number of pages6
JournalNeuroscience Research
Volume72
Issue number2
DOIs
Publication statusPublished - 2012 Feb

Keywords

  • Atrogin-1
  • Dysferlinopathy
  • Muscular dystrophy
  • Osmotic pump
  • P38
  • Poloxamer 188 (P188)

ASJC Scopus subject areas

  • Neuroscience(all)

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