Early raise of BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants

Laura Musazzi, Annamaria Cattaneo, Daniela Tardito, Alessandro Barbon, Massimo Gennarelli, Sergio Barlati, Giorgio Racagni, Maurizio Popoli

Research output: Contribution to journalArticle

Abstract

Background: The neurotrophin BDNF has been implicated in the regulation of neuroplasticity, gene expression, and synaptic function in the adult brain, as well as in the pathophysiology of neuropsychiatric disorders and the mechanism of action of antidepressants. Antidepressant treatments have been shown to increase the expression of BDNF mRNA, although the changes measured were found to be different depending on various factors. A few studies only have measured levels of BDNF protein after antidepressant treatments, and poor correlation was found between mRNA and protein changes. We studied the time course of expression of BDNF mRNA and protein during drug treatments, in order to elucidate the temporal profile of regulation of this effector and whether mRNA and protein levels correlate. Rat groups were treated for 1, 2 or 3 weeks with fluoxetine or reboxetine; in additional groups drug treatment was followed by a washout week (3+1). Total BDNF mRNA was measured by Real Time PCR, pro- and mature BDNF proteins were measured by Western blot. Results: We found that mature BDNF protein is induced more rapidly than mRNA, by both drugs in hippocampus (weeks 1-2) and by reboxetine in prefrontal/frontal cortex (week 1). The temporal profile of BDNF protein expression was largely inconsistent with that of mRNA, which followed the protein induction and reached a peak at week 3. Conclusion: These results suggest that BDNF protein is rapidly elevated by antidepressant treatments by posttranscriptional mechanisms, and that induction of BDNF mRNA is a slower process.

Original languageEnglish
Article number48
JournalBMC Neuroscience
Volume10
DOIs
Publication statusPublished - May 13 2009

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ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)

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