Effects of corticosterone and antidepressants fluoxetine and amitriptyline on the expression of neurotrophic factors in rat astrocytoma C6 cells

Introduction. Depression is the most common mental illness. The etiopathogenesis of depression and the mechanisms of action of antidepressants remain poorly understood. Accumulating evidence indicates the involvement of neurotrophic factors (NTFs) in depression and the effects of antidepressants. Chronic stress is a risk factor for depression and leads to decreased NTF levels in several brain regions. The effects of chronic glucocorticoid and antidepressant exposure on NTF expression in astrocytes remains largely unexplored. The aim of this study was to evaluate the effects of corticosterone at stress concentration and antidepressants on the expression of associated with depression or antidepressant action NTFs in C6 cells. Material and methods. Cultured rat C6 astrocytoma cells were used. Serum-free culture medium was supplemented with corticosterone at basal (0.1 μM) or stress (1 μM) concentrations, with amitriptyline (25 μM), or fluoxetine (10 μM) once or for 7 days. After 24 h, BDNF, NGF, VEGF, and S100β mRNA levels were assessed using real-time RT-PCR. Results. Corticosterone (1 μM) stimulated BDNF expression both acutely and chronically. Stimulation of NGF and S100β expression and suppression of VEGF expression were observed only with chronic exposure. Antidepressants stimulated BDNF and NGF expression only with chronic exposure and only at basal corticosterone concentration. Both amitriptyline and fluoxetine increased VEGF expression during chronic exposure to both concentrations of corticosterone. Conclusion. These data demonstrate that corticosterone at stress level regulates the expression of depression-associated NTFs in C6 cells. These results may reflect the neuroprotective role of astrocytes during stress, the involvement of astrocytes in the therapeutic effects of antidepressants, and can be used to develop cell models to study the mechanisms of stress effects on the central nervous system and to test compounds with potential antidepressant activity.