Correction of humoral derangements from mutant superoxide dismutase 1 spinal cord

Yun Sook Kim, Tara Martinez, Deepa M. Deshpande, Jennifer Drummond, Katie Provost-Javier, Ariel Williams, Julie McGurk, Nicholas Maragakis, Hongjun Song, Guo Li Ming, Douglas A. Kerr

Research output: Contribution to journalArticle

Abstract

Objective: We sought to define molecular and cellular participants that mediate motor neuron injury in amyotrophic lateral sclerosis using a coculture system. Methods: We cocultured embryonic stem cell-derived motor neurons with organotypic slice cultures from wild-type or SOD1G93A (MT) mice. We examined axon lengths and cell survival of embryonic stem cell-derived motor neurons. We defined and quantified the humoral factors that differed between wild-type and MT organotypic cultures, and then corrected these differences in cell culture. Results: MT spinal cord organotypic slices were selectively toxic to motor neurons as defined by axonal lengths and cell survival. MT spinal cord organotypic slices secreted higher levels of nitric oxide, interleukin (IL)-1β, IL-6, and IL-12p70 and lower levels of vascular endothelial growth factor. The toxicity of MT spinal cord organotypic cultures was reduced and axonal lengths were restored to neat normal by coculturing in the presence of reactive oxygen species scavenger, vascular endothelial growth factor, and neutralizing antibodies to IL-1β, IL-6, and IL-12. Interpretation: MT spinal cord organotypic cultures overexpress certain factors and underexpress others, creating a nonpermissive environment for cocultured motor neurons. Correction of these abnormalities as a group, but not individually, restores axonal length to near normal. Such a "cocktail" approach to the treatment of amyotrophic lateral sclerosis should be investigated further.

Original languageEnglish (US)
Pages (from-to)716-728
Number of pages13
JournalAnnals of neurology
Volume60
Issue number6
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Correction of humoral derangements from mutant superoxide dismutase 1 spinal cord'. Together they form a unique fingerprint.

  • Cite this

    Kim, Y. S., Martinez, T., Deshpande, D. M., Drummond, J., Provost-Javier, K., Williams, A., McGurk, J., Maragakis, N., Song, H., Ming, G. L., & Kerr, D. A. (2006). Correction of humoral derangements from mutant superoxide dismutase 1 spinal cord. Annals of neurology, 60(6), 716-728. https://doi.org/10.1002/ana.21034