Neuronal activity promotes myelination via a cAMP pathway

Misti Malone, Devin Gary, In Hong Yang, Anna Miglioretti, Thierry Houdayer, Nitish Thakor, John Mcdonald

Research output: Contribution to journalArticle

Abstract

Neuronal activity promotes myelination in vivo and in vitro. However, the molecular events that mediate activity-dependent myelination are not completely understood. Seven, daily 1 h sessions of patterned electrical stimulation (ESTIM) promoted myelin segment formation in mixed cultures of dorsal root ganglion (DRG) neurons and oligodendrocytes (OLs); the increase in myelination was frequency-dependent. Myelin segment formation was also enhanced following exposure of DRGs to ESTIM prior to OL addition, suggesting that ESTIM promotes myelination in a manner involving neuron-specific signaling. Cyclic adenosine monophosphate (cAMP) levels in DRGs were increased three-fold following ESTIM, and artificially increasing cAMP mimicked the ability of ESTIM to promote myelination. Alternatively, inhibiting the cAMP pathway suppressed ESTIM-induced myelination. We used compartmentalized, microfluidic platforms to isolate DRG soma from OLs and assessed cell-type specific effects of ESTIM on myelination. A selective increase or decrease in DRG cAMP levels resulted in enhanced or suppressed myelination, respectively. This work describes a novel role for the cAMP pathway in neurons that results in enhanced myelination.

Original languageEnglish (US)
Pages (from-to)843-854
Number of pages12
JournalGlia
Volume61
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Electrical stimulation
  • Frequency
  • Microfluidic chamber
  • Myelin
  • Oligodendrocyte

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Malone, M., Gary, D., Yang, I. H., Miglioretti, A., Houdayer, T., Thakor, N., & Mcdonald, J. (2013). Neuronal activity promotes myelination via a cAMP pathway. Glia, 61(6), 843-854. https://doi.org/10.1002/glia.22476