Electrical stimulation promotes nerve growth factor-induced neurite outgrowth and signaling

• Published in: Biochimica et biophysica acta Vol. 1830; no. 8; pp. 4130 - 4136
• Main Authors: Chang, Yu-Jung, Hsu, Che-Ming, Lin, Chia-Hua, Lu, Michael Shiang-Cheng, Chen, Linyi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2013
• Subjects: Animals; collagen; Electric Stimulation; Electrical stimulation; electrical treatment; Extracellular Signal-Regulated MAP Kinases - metabolism; genes; Nerve growth factor; Nerve Growth Factor - pharmacology; nerve tissue; Neurite outgrowth; Neurites - drug effects; Neurites - physiology; neurodevelopment; PC12 Cells; Phosphorylation; protein kinase; protein kinase C; Rats; Signal Transduction - drug effects; therapeutics; Electrical stimulation; Nerve growth factor; Neurite outgrowth
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.04.007

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. 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. 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. It is likely that ES promotes NGF-induced neurite outgrowth through modulating the activity of ERK1/2. Findings from this study suggest that combining ES and NGF provides a promising strategy for promoting neurite outgrowth. •Electrical stimulation promotes nerve growth factor (NGF)-induced neurite outgrowth.•Electrical stimulation activates protein kinase C and promotes NGF-induced pERK1/2.•Combining electrical stimulation and NGF may promote neural regeneration.