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


CONCLUSIONS
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.
Musazzi
Laura
L
Center of Neuropharmacology-Department of Pharmacological Sciences, University of Milan, Milan, Italy. laura.musazzi@unimi.it
Cattaneo
Annamaria
A
Tardito
Daniela
D
Barbon
Alessandro
A
Gennarelli
Massimo
M
Barlati
Sergio
S
Racagni
Giorgio
G
Popoli
Maurizio
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D018709:Statistics, Nonparametric; D014158:Transcription, Genetic / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D009025:Morpholines; D012333:RNA, Messenger; D000077593:Reboxetine; D017367:Selective Serotonin Reuptake Inhibitors