title: Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax.
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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biotechnology and Molecular Science, University of Insubria, Varese, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tognoli
authors.forename: Federica
authors.initials: F
authors.lastname: Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Cola
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baj
authors.forename: Enrico
authors.initials: E
authors.lastname: Tongiorgi
authors.forename: Genciana
authors.initials: G
authors.lastname: Terova
authors.forename: Marco
authors.initials: M
authors.lastname: Saroglia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bernardini
authors.forename: Rosalba
authors.initials: R
authors.lastname: Gornati
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001492:Bass; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity; D017385:Sequence Homology; D013315:Stress, Psychological / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D020033:Protein Isoforms; D012333:RNA, Messenger