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


RESULTS
Cultured 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.


CONCLUSIONS
This 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.
Donnici
Lorena
L
Center of Neuropharmacology, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Italy. lory80@hotmail.com
Tiraboschi
Ettore
E
Tardito
Daniela
D
Musazzi
Laura
L
Racagni
Giorgio
G
Popoli
Maurizio
M
D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D045744:Cell Line, Tumor; D003891:Desipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077593:Reboxetine; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D019208:Brain-Derived Neurotrophic Factor; D009025:Morpholines; D012333:RNA, Messenger; D005473:Fluoxetine; D000077593:Reboxetine; D003891:Desipramine