Beyond good and evil: A putative continuum-sorting hypothesis for the functional role of proBDNF/BDNF-propeptide/mBDNF in antidepressant treatment

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  • Cassiano R A F Diniz, School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, Campus USP, Ribeirão Preto, SP 14040-904, Brazil. Electronic address:
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  • Plinio C Casarotto, School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil; Neuroscience Center - HILife, University of Helsinki, Finland.
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  • Leonardo Resstel, School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil.
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  • Sâmia R L Joca

Depression and posttraumatic stress disorder are assumed to be maladaptive responses to stress and antidepressants are thought to counteract such responses by increasing BDNF (brain-derived neurotrophic factor) levels. BDNF acts through TrkB (tropomyosin-related receptor kinase B) and plays a central role in neuroplasticity. In contrast, both precursor proBDNF and BDNF propeptide (another metabolic product from proBDNF cleavage) have a high affinity to p75 receptor (p75R) and usually convey apoptosis and neuronal shrinkage. Although BDNF and proBDNF/propeptide apparently act in opposite ways, neuronal turnover and remodeling might be a final common way that both act to promote more effective neuronal networking, avoiding neuronal redundancy and the misleading effects of environmental contingencies. This review aims to provide a brief overview about the BDNF functional role in antidepressant action and about p75R and TrkB signaling to introduce the "continuum-sorting hypothesis." The resulting hypothesis suggests that both BDNF/proBDNF and BDNF/propeptide act as protagonists to fine-tune antidepressant-dependent neuroplasticity in crucial brain structures to modulate behavioral responses to stress.

Original languageEnglish
JournalNeuroscience & Biobehavioral Reviews
Pages (from-to)70-83
Number of pages14
Publication statusPublished - 2018

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