title: Electrical stimulation promotes nerve growth factor-induced neurite outgrowth and signaling.
abstract: BACKGROUND
  Neurotrophins are important regulators for neural development and regeneration. Nerve growth factor (NGF) therapy has been tested in various models of neural injury and degeneration. However, whether NGF can reach target tissues and maintain effective concentration for a certain period of time remains uncertain. To facilitate neural regeneration, we investigate the possibility of combining NGF and electrical stimulation (ES) in promoting neurite outgrowth, an essential process during neural regeneration.
  
  
  METHODS
  PC12 cells were seeded on collagen and indium tin oxide (ITO)-coated area on the transparent conductive devices. Cells were then subjected to the combination of ES and NGF treatment. Neurite outgrowth was compared.
  
  
  RESULTS
  Our findings suggest that ES of 100mV/mm together with NGF provides optimal effect on neurite outgrowth of PC12 cells. ES increases NGF-induced neurite length but reduces neurite branching, indicative of its primary effect on neurite elongation instead of initiation. One mechanism that ES enhances neurite outgrowth is through increasing NGF-induced phosphorylation of ERK1/2 (pERK1/2) and expression of Egr1 gene. ES has previously been demonstrated to increase the activity of protein kinase C (PKC). Our result indicates that activating PKC further increases NGF-induced pERK1/2 and thus neurite outgrowth.
  
  
  CONCLUSIONS
  It is likely that ES promotes NGF-induced neurite outgrowth through modulating the activity of ERK1/2.
  
  
  CONCLUSIONS
  Findings from this study suggest that combining ES and NGF provides a promising strategy for promoting neurite outgrowth.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Chang
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Hsu
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Lin
authors.forename: Michael Shiang-Cheng
authors.initials: MS
authors.lastname: Lu
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D020932:Nerve Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases