title: Electrically induced brain-derived neurotrophic factor release from Schwann cells.
abstract: Regulating the production of brain-derived neurotrophic factor (BDNF) in Schwann cells (SCs) is critical for their application in traumatic nerve injury, neurodegenerative disorders, and demyelination disease in both central and peripheral nervous systems. The present study investigated the possibility of using electrical stimulation (ES) to activate SCs to release BDNF. We found that short-term ES was capable of promoting BDNF production from SCs, and the maximal BDNF release was achieved by ES at 6 V (3 Hz, 30 min). We further examined the involvement of intracellular calcium ions ([Ca2+]i) in the ES-induced BDNF production in SCs by pharmacological studies. We found that the ES-induced BDNF release required calcium influx through T-type voltage-gated calcium channel (VGCC) and calcium mobilization from internal calcium stores, including inositol triphosphate-sensitive stores and caffeine/ryanodine-sensitive stores. In addition, calcium-calmodulin dependent protein kinase IV (CaMK IV), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) were found to play important roles in the ES-induced BDNF release from SCs. In conclusion, ES is capable of activating SCs to secrete BDNF, which requires the involvement of calcium influx through T-type VGCC and calcium mobilization from internal calcium stores. In addition, activation of CaMK IV, MAPK, and CREB were also involved in the ES-induced BDNF release. The findings indicate that ES can improve the neurotrophic ability in SCs and raise the possibility of developing electrically stimulated SCs as a source of cell therapy for nerve injury in both peripheral and central nervous systems.
authors.affiliation: Institute of Orthopaedics, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Beier
authors.initials: B
authors.lastname: Luo
authors.forename: Jinghui
authors.initials: J
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Lu
authors.forename: Xueyu
authors.initials: X
authors.lastname: Hu
authors.forename: Zhuojing
authors.initials: Z
authors.lastname: Luo
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001917:Brachial Plexus / Q000166:cytology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology; D012844:Sincalide / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D009418:S100 Proteins; D050882:CREB-Binding Protein; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D012844:Sincalide; D002118:Calcium
keywords: brain-derived neurotrophic factor; calcium; calcium-calmodulin dependent protein kinase; electrical stimulation; mitogen-activated protein kinase