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

Novozhenova A.N.; Dolotov O.V.; Grivennikov I.A.

doi:https://doi.org/10.17116/molgen202543042111

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.

Keywords:

stress

glucocorticoids

corticosterone

depression

antidepressants

astrocytes

rat astrocytoma C6

neurotrophic factors

Authors:

Novozhenova A.N.

Skolkovo Institute of Science and Technology

Dolotov O.V.

National Research Center “Kurchatov Institute” — Laboratory of Molecular Neurogenetics and Innate Immunity;
Lomonosov Moscow State University, Faculty of Biology

ORCID: 0000-0003-3187-6331

Grivennikov I.A.

National Research Center “Kurchatov Institute” — Laboratory of Molecular Neurogenetics and Innate Immunity

ORCID: 0000-0003-0128-5661

Received:

03.10.2025

Accepted:

23.10.2025

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