Time-dependent biphasic modulation of human BDNF by antidepressants in neuroblastoma cells

Lorena Donnici,Daniela Tardito,Ettore Tiraboschi,Giorgio Racagni,Maurizio Popoli,Laura Musazzi

doi:10.1186/1471-2202-9-61

Abstract

BackgroundRecent rodent studies reported that antidepressant treatments affect the expression of brain-derived neurotrophic factor (BDNF) mRNA in a way that is dependent on treatment duration, by selective modulation of different BDNF transcripts. However, no data are available for the human BDNF gene. We studied the effect of different antidepressants on BDNF mRNA expression in human neuroblastoma SH-SY5Y cells.ResultsCultured cells were treated with the antidepressants fluoxetine, reboxetine and desipramine for different time lengths (6, 24, 48 hours). Expression of total BDNF mRNA was analyzed by reverse transcription PCR and levels of different BDNF transcripts were detected by hemi-nested PCR with specific primers.Short-term treatment (6 hours) with reboxetine or desipramine reduced total BDNF, whereas long-term treatment (48 hours) significantly increased total BDNF mRNA levels. These changes were accounted for by differential regulation of BDNF IV and VIa/b transcripts. Fluoxetine showed no significant effects.ConclusionThis is the first study showing biphasic changes in the expression of total and specific BDNF transcripts in human cells following antidepressant treatments. These findings suggest that biphasic induction of BDNF by antidepressants could be a feature common to rodents and humans and encourage the use of SH-SY5Y cells as a tool for investigation of drug effects on human genes.

Highlights

Recent rodent studies reported that antidepressant treatments affect the expression of brain-derived neurotrophic factor (BDNF) mRNA in a way that is dependent on treatment duration, by selective modulation of different BDNF transcripts
In order to characterize the effects of different antidepressants on total human BDNF mRNA expression, SH-SY5Y neuroblastoma cells were treated with FLX, RBX or DMI for 6 h, 24 or 48 hours, as in recent studies assessing the long-term effects of antidepressants in cultured cells [16,17]
RBX and DMI exerted a biphasic effect on BDNF mRNA: BDNF mRNA expression was reduced after 6 hours treatment with RBX or DMI, returned to basal level at 24 hours and was significantly increased after 48 hours (Fig. 2A)

Summary

Introduction

Recent rodent studies reported that antidepressant treatments affect the expression of brain-derived neurotrophic factor (BDNF) mRNA in a way that is dependent on treatment duration, by selective modulation of different BDNF transcripts. It has been shown that BDNF expression and/or function is impaired in major depression or following stress paradigms, while it is up-regulated by physical exercise and antidepressants. Different and sometimes conflicting findings have been reported [2], showing that antidepressants change total BDNF expression level depending on length of the treatment and time interval following administration. Recent studies showed that different drugs, lengths of treatment and drug/physical exercise combination, as well as stress paradigms, may selectively influence the transcription of specific BDNF transcripts in rodents [6,9,10,11,12]

Results

Discussion

Conclusion