Journal of Molecular Neuroscience

, Volume 34, Issue 3, pp 193–200

Progesterone Pretreatment Enhances Serotonin-Stimulated BDNF Gene Expression in Rat C6 Glioma Cells Through Production of 5α-Reduced Neurosteroids

Authors

    • Department of PharmacologyTokushima University School of Medicine
  • Song Her
    • Department of BioimagingKorea Basic Science Institute
Article

DOI: 10.1007/s12031-007-9034-6

Cite this article as:
Morita, K. & Her, S. J Mol Neurosci (2008) 34: 193. doi:10.1007/s12031-007-9034-6

Abstract

Tricyclic antidepressants and selective serotonin reuptake inhibitors are considered in theory to induce the outflow of neurotransmitters, norepinephrine, and serotonin from the synapses as a consequence of inhibiting their reuptake into the nerve terminals, resulting in the stimulation of glial cells surrounding the synapses in the brain. Then, we have investigated the direct actions of neurotransmitters on glial cell metabolism and function using rat C6 glioma cells as an in vitro model system and suggested that these neurotransmitters induce their differentiation probably through the production of 5α-reduced neurosteroids. On the other hand, the stimulation of the glioma cells with serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) gene expression, which may be closely related to the beneficial effects of antidepressant drugs. In the present study, to evaluate BDNF expression in differentiated glial cells, the glioma cells were pretreated with progesterone, and the effect of serotonin on BDNF messenger RNA levels in these cells was examined. Progesterone pretreatment enhanced the stimulatory action of serotonin on BDNF gene expression, and the enhancement of serotonin action observed in the cells pretreated with progesterone was almost completely abolished by finasteride, an inhibitor of the enzyme involved in the production of 5α-reduced neurosteroids. These findings propose the possibility that neurosteroid-mediated glial cell differentiation may result in the enhancement of serotonin-stimulated BDNF gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain, and hence, leading to the improvement of mood disorders and other symptoms in depressive patients.

Keywords

Progesterone metabolitesNeuroactive steroidsSerotonergic stimulationNeurotrophic factorsGlial cell differentiation

Copyright information

© Humana Press Inc. 2008