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 language | English (US) |
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Pages (from-to) | 843-854 |
Number of pages | 12 |
Journal | Glia |
Volume | 61 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2013 |
Keywords
- Electrical stimulation
- Frequency
- Microfluidic chamber
- Myelin
- Oligodendrocyte
ASJC Scopus subject areas
- Neurology
- Cellular and Molecular Neuroscience