Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis

Chandler L. Walker, Rena M. Meadows, Stephanie Merfeld-Clauss, Yansheng Du, Keith L. March, Kathryn J. Jones

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ?47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective: To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and postsynaptic acetylcholine receptors (AchR) by -bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200l ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with -bungarotoxin in gastrocnemius muscle. Results: Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions: Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS.

Original languageEnglish (US)
Pages (from-to)621-627
Number of pages7
JournalRestorative Neurology and Neuroscience
Volume36
Issue number5
DOIs
StatePublished - Jan 1 2018

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Keywords

  • ALS
  • Amyotrophic lateral sclerosis
  • adipose-derived stem cells
  • conditioned medium
  • neuromuscular junctions

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

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