The Effect of Erythropoietin on Neurotrophic Factors in N9 Murine Microglial Cells

Aim: In this study, we investigated whether interferon gamma (IFNgamma), lipopolysaccharides (LPS) and amyloidbeta (AMY beta), as toxic stimulator agents, and erythropoietin (EPO), as a neurotrophic agent, have an effect on the production of the following neurotrophic factors in the N9 murine microglia cell line: neurotrophin 3(NT3), neurotrophin 4 (NT4), and brain-derived neurotrophic factor (BDNF).Materials and Methods: Microglial cells were incubated with 50 mu g/ml AMY beta, or 1 mu g/ml of LPS plus 100U/ml recombinant murine IFN gamma, and/or one of three different concentrations (0.1, 1.0, and 5.0 U/ml) of recombinant mouse EPO for 24 h.Results: EPO 0.1 U/ml dose significantly increased NT4 levels compared to EPO 5.0 U/ml dose (P 0.05).EPO, in all doses, and AMY beta significantly induced NT4 secretion in microglias, while BDNF and NT3 were not changed by AMY beta or EPO. LPS + IFNgamma alone did not change neurotrophic factor levels in any group. However,EPO with LPS and IFN gamma induced NT4 secretion, especially the 5.0 U/ml dose of EPO.Conclusions: NT4 secretion, which was markedly induced by exposure to both AMY beta and EPO in N9 murinemicroglias, may be an important result for neuronal survival. These results suggest that inflammatory mechanisms in microglia may also involve the neuroprotective response of these cells; this may be a promisingarea of study of neurodegenerative processes.