title: Neuronal activity promotes myelination via a cAMP pathway.
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.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Misti
authors.initials: M
authors.lastname: Malone
authors.forename: Devin
authors.initials: D
authors.lastname: Gary
authors.forename: In Hong
authors.initials: IH
authors.lastname: Yang
authors.forename: Anna
authors.initials: A
authors.lastname: Miglioretti
authors.forename: Thierry
authors.initials: T
authors.lastname: Houdayer
authors.forename: Nitish
authors.initials: N
authors.lastname: Thakor
authors.forename: John
authors.initials: J
authors.lastname: McDonald
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000242:Cyclic AMP