Astrocyte and muscle-derived secreted factors differentially regulate motoneuron survival

Anna R. Taylor, David J. Gifondorwa, Jason Newbern, Mac B. Robinson, Jane L. Strupe, David Prevette, Ronald W. Oppenheim, Carolanne E. Milligan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

During development, motoneurons (MNs) undergo a highly stereotyped, temporally and spatially defined period of programmed cell death (PCD), the result of which is the loss of 40-50% of the original neuronal population. Those MNs that survive are thought to reflect the successful acquisition of limiting amounts of trophic factors from the target. In contrast, maturation of MNs limits the need for target-derived trophic factors, because axotomy of these neurons in adulthood results in minimal neuronal loss. It is unclear whether MNs lose their need for trophic factors altogether or whether, instead, they come to rely on other cell types for nourishment. Astrocytes are known to supply trophic factors to a variety of neuronal populations and thus may nourish MNs in the absence of target-derived factors. We investigated the survival-promoting activities of muscle- and astrocyte-derived secreted factors and found that astrocyte-conditioned media (ACM) was able to save substantially more motoneurons in vitro than muscle-conditioned media (MCM). Our results indicate that both ACM and MCM are significant sources of MN trophic support in vitro and in ovo, but only ACM can rescue MNs after unilateral limb bud removal. Furthermore, we provide evidence suggesting that MCM facilitates the death of a subpopulation of MNs in a p75NTR - and caspase-dependent manner; however, maturation in ACM results in MN trophic independence and reduced vulnerability to this negative, pro-apoptotic influence from the target.

Original languageEnglish (US)
Pages (from-to)634-644
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number3
DOIs
StatePublished - Jan 17 2007
Externally publishedYes

Fingerprint

Motor Neurons
Astrocytes
Conditioned Culture Medium
Muscles
Limb Buds
Axotomy
Caspases
Population
Cell Death
Neurons

Keywords

  • Amyotrophic lateral sclerosis
  • Apoptosis
  • Caspase
  • p75NTR
  • Programmed cell death
  • SMA
  • Trophic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Taylor, A. R., Gifondorwa, D. J., Newbern, J., Robinson, M. B., Strupe, J. L., Prevette, D., ... Milligan, C. E. (2007). Astrocyte and muscle-derived secreted factors differentially regulate motoneuron survival. Journal of Neuroscience, 27(3), 634-644. https://doi.org/10.1523/JNEUROSCI.4947-06.2007

Astrocyte and muscle-derived secreted factors differentially regulate motoneuron survival. / Taylor, Anna R.; Gifondorwa, David J.; Newbern, Jason; Robinson, Mac B.; Strupe, Jane L.; Prevette, David; Oppenheim, Ronald W.; Milligan, Carolanne E.

In: Journal of Neuroscience, Vol. 27, No. 3, 17.01.2007, p. 634-644.

Research output: Contribution to journalArticle

Taylor, AR, Gifondorwa, DJ, Newbern, J, Robinson, MB, Strupe, JL, Prevette, D, Oppenheim, RW & Milligan, CE 2007, 'Astrocyte and muscle-derived secreted factors differentially regulate motoneuron survival', Journal of Neuroscience, vol. 27, no. 3, pp. 634-644. https://doi.org/10.1523/JNEUROSCI.4947-06.2007
Taylor, Anna R. ; Gifondorwa, David J. ; Newbern, Jason ; Robinson, Mac B. ; Strupe, Jane L. ; Prevette, David ; Oppenheim, Ronald W. ; Milligan, Carolanne E. / Astrocyte and muscle-derived secreted factors differentially regulate motoneuron survival. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 3. pp. 634-644.
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