title: The mood stabilizer valproic acid induces proliferation and myelination of rat Schwann cells.
abstract: Schwann cells (SCs) within peripheral nerve respond robustly after exposure to neurotrophic factors. Recent results have revealed that valproic acid (VPA), at a clinically relevant therapeutic concentration, produces effects similar to neurotrophic factors, and promotes neurite growth and cell survival. We hypothesized that VPA could also induce Schwann cell response. In this study, we sought to determine how pure Schwann cells responded to VPA by evaluating for proliferation, expression of S-100, growth cone-associated protein 43 (GAP-43), myelin-associated glycoprotein (MAG), and myelin basic protein (MBP). Immunohistochemistry demonstrated that the Schwann cells were positive for S-100, GAP-43, MAG, and MBP greater than 99% of the experimental cells. The rate of proliferation was increased in experimental cells from MTT assay and Bromodeoxyuridine/DAPI double staining. Furthermore, Western blot showed an up-regulation in GAP-43, MAG and MBP protein expression in experimental cells, respectively. We also found that mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2 pathway was involved in the enhanced cell proliferation of Schwann cells evoked by VPA. This study provides novel information regarding Schwann cell response to VPA, which might help the understanding of VPA-based treatment for peripheral nerve injury.
authors.affiliation: Department of Hand Surgery & Microsurgery, Affiliated Pu Ai Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan City, Hu Bei Province, People's Republic of China.
authors.forename: Wu
authors.initials: W
authors.lastname: Fei
authors.forename: Yu
authors.initials: Y
authors.lastname: Aixi
authors.forename: Xing
authors.initials: X
authors.lastname: Danmou
authors.forename: Kan
authors.initials: K
authors.lastname: Wusheng
authors.forename: Peng
authors.initials: P
authors.lastname: Zhengren
authors.forename: Rao
authors.initials: R
authors.lastname: Ting
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D018692:Antimanic Agents; D014635:Valproic Acid