Abstract
BackgroundStress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions.ResultsWe provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%.ConclusionThe high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.
Highlights
Stress involves alterations of brain functioning that may precipitate to mood disorders
To determine the D. labrax Brain Derived Neurotrophic Factor (BDNF) gene exon/intron boundaries and identify the mRNAs transcribed from the gene, we performed a combination of 5’ and 3’ rapid amplification of cDNA ends (5’ and 3’ Rapid Amplification of cDNA Ends (RACE)), RT-PCR and bioinformatic analysis
In analogy with zebrafish and pufferfish, in D. labrax the BDNF coding sequence is contained in the exon 2 and this tract resulted highly conserved with respect to other vertebrate species (D. rerio 84%, F. rubripes 91%, H. sapiens 77%, M. musculus 78%, R. norvegicus 78%, )
Summary
Stress involves alterations of brain functioning that may precipitate to mood disorders. Regulation of BDNF is complex and may reflect stress-specific mechanisms and hormonal and emotional responses For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. Since alterations in BDNF expression were found in response to emotions such as anxiety or fear in rodents [22] and BDNF affects emotional preferences in humans [23], it remains to be determined how the stress itself or the associated behavioral responses contribute in mediating these changes In this view, it is interesting to use as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions
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