Prevention Of Streptozotocin-Induced Neuro-2a Cell Death By C8-B4 Microglia Transformed With Repetitive Low-Dose Lipopolysaccharide

Diabetes-associated neuronal dysfunction (DAND) is one of the serious complications of diabetes, but there is currently no remedy for it. Streptozotocin [2-deoxy-2-(3-methy1-3-nitrosoureido) D-glucopyranose; STZ] is one of the most well-established diabetes inducers and has been used in vivo and in vitro DAND models. The aim of the present study was to demonstrate that C8-B4 microglia transformed by the stimulus of repetitive low-dose lipopolysaccharide (LPSx3-microglia) prevent STZ-induced Neuro-2a neuronal cell death in vitro. The ELISA results showed that neurotrophin-4/5 (NT-4/5) secretion was promoted in LPSx3-microglia and the cell viability assay with trypan blue staining revealed that the culture supernatant of LPSx3-microglia prevented STZ-induced neuronal cell death. In addition, reverse transcription-quantitative PCR showed that neurons treated with the culture supernatant of LPSx3-microglia promoted the gene expression of B-cell lymphoma-extra large and glucose-dependent insulinotropic polypeptide receptor. Furthermore, the inhibition of tyrosine kinase receptor B, a receptor of NT-4/5, suppressed the neuroprotective effect of LPSx3-microglia. Taken together, the present study demonstrated that LPSx3-microglia prevent STZ-induced neuronal death and that NT-4/5 may be involved in the neuroprotective mechanism of LPSx3-microglia.