Fluoxetine stimulates glial cell line-derived neurotrophic factor synthesis and release in cultured rat astrocytes

Objective To explore the effects of fluoxetine on glial cell line-derived neurotrophic factor (GDNF) synthesis and release in cultured rat astrocytes. Methods The MTT assay were used to evaluate cell viability, the expression of GDNF mRNA were detected with real-time PCR. The level of GDNF in cell-conditioned media was measured using enzyme linked immunosorbent assay (ELISA). Results (1) The cell viability was significantly decreased when the concentration of fluoxetine was more than 35 μmol/L (P<0.01 or P<0. 05). (2) When the cells were treated with the 10 μmol/L fluoxetine for different time, the level of GDNF in cell-conditioned media of the 48 hour group [(68±13) fg/L] was significantly higher than that of the 0, 6, 12, 24 hour group [(32±11), (34±12), (41±17) and (45±13) fg/L] (P<0.01). (3) When the cells were treated with the different concentration of fluoxetine for 48 hour, the level of GDNF in cell-conditioned media of 10 μmol/L group[(64±17) fg/L] was significantly higher than that of 0 μmol/L and 1 μmol/L groups[(39±15), (39±18) fg/L] (P<0.05). (4) When the cells were treated at a range of concentrations of fluoxetine for 48 hour, the GDNF was also significantly released by astrocytes after with draual of fluoxetine for 24 hours, (P<0.01or P<0.05). (5) After the cells were treated with the different concentrations of fluoxetine for 24 hour, the expression of GDNF mRNA in 10 μmol/L and 20 μmol/L groups [(0.008 1±0.001 1), (0.006 3±0.000 3)] were significantly higher than that in 0 μmol/L, 1 μmol/L and 5 μmol/L groups [(0.003 1±0.000 7), (0.003 9±0.000 3),(0.004 1±0.000 2)]. Conclusion The results suggest that fluoxetine could stimulate GDNF release from astrocytes, which might underlie it's neuroprotective properties. Key words: Fluoxetine;  Astrocytes;  Glial cell line-derived neurotrophic factor