Glial cell line-derived neurotrophic factor promotes olfactory ensheathing cells migration.

KEY WORDSGDNF; olfactory ensheathing cells; migration; neural regenera-tionABSTRACTOlfactory ensheathing cells (OECs) are a unique type ofmacroglia with axonal growth-promoting properties. Themigrating ability of OECs in CNS is essential for neuralregeneration. However, little is known about the extracellu-lar and intracellular factors that regulate OEC migration.In the present study, we examined the effects of glial cellline-derived neurotrophic factor (GDNF) on OECs migra-tion. Initially, the ‘‘scratch’’ migration assay, Boyden cham-ber assay, and explant migration assay showed that GDNFcould promote OECs migration in vitro. Treatment of OECswith GDNF also induced cytoskeleton reorganization andup-regulated expression of cytoskeleton proteins. GDNF-induced OECs migration was demonstrated depending onGFRa-1 and Ret receptor, and activation of JNK and Srcsignaling cascades. Furthermore, GDNF was found to pro-mote implanted OECs migration in a spinal cord hemisec-tion injury model. Together, we report, to our knowledge forthe first time, that GDNF stimulate OECs migration in vitroandinvivo.