Liraglutide Protects Neurite Outgrowth of Cortical Neurons Under Oxidative Stress though Activating the Wnt Pathway

Abstract

BackgroundNeurogenesis including neurite outgrowth is important for brain plasticity under physiological conditions and in brain repair after injury. Liraglutide has been found to have neuroprotective action in the risk of central nervous system disease. However, the effect and the potential mechanism of liraglutide-induced neurite outgrowth in primary cortical neurons under oxidative stress remain poorly documented. MethodsIn the text, H2O2 was used to mimic ischemia injury in primary cortical neurons. The viability and apoptosis of cell was assessed by Cell Counting Kit-8 and Hoechst 33342. Immunofluorescence method was used to examine the effect of liraglutide on neurite outgrowth in cortical neuron under H2O2 condition. Then, the potential mechanisms involving the Wnt pathway were investigated. The expression of β-catenin, c-myc, and cyclin D1 was determined using quantitative real-time polymerase chain reaction and Western blot. ResultsLiraglutide significantly increased the viability and alleviated the apoptosis rate of cortical neurons induced by H2O2. Next, liraglutide promoted neurite outgrowth, which could be partially inhibited by the Wnt pathway inhibitor Xav939. Besides, liraglutide induced an increase of β-catenin, c-myc, and cyclin D1 levels, which could also be blocked in the presence of Xav939. ConclusionsThese results illustrate that liraglutide exerts neurotrophin-like activity in cortical neurons under oxidative stress condition, partly through activating the Wnt pathway.