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Open Access Highly Accessed Research article

Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax

Chiara Tognoli1, Federica Rossi1, Francesco Di Cola2, Gabriele Baj2, Enrico Tongiorgi2, Genciana Terova1, Marco Saroglia1, Giovanni Bernardini13 and Rosalba Gornati13*

Author Affiliations

1 Department of Biotechnology and Molecular Science, University of Insubria, Varese-Italy

2 Department for Life Sciences, BRAIN Centre for Neuroscience, University of Trieste, Trieste-Italy

3 Centro di Ricerca Interuniversitario Politecnico di Milano e Università dell'Insubria "The Protein Factory", Italy

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BMC Neuroscience 2010, 11:4  doi:10.1186/1471-2202-11-4

Published: 14 January 2010

Abstract

Background

Stress 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.

Results

We 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%.

Conclusion

The 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.