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

TY - JOUR

T1 - Beyond good and evil

T2 - A putative continuum-sorting hypothesis for the functional role of proBDNF/BDNF-propeptide/mBDNF in antidepressant treatment

AU - Diniz, Cassiano R A F

AU - Casarotto, Plinio C

AU - Resstel, Leonardo

AU - Joca, Sâmia R L

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1016/j.neubiorev.2018.04.001

DO - 10.1016/j.neubiorev.2018.04.001

M3 - Review

C2 - 29626490

SN - 0149-7634

VL - 90

SP - 70

EP - 83

JO - Neuroscience & Biobehavioral Reviews

JF - Neuroscience & Biobehavioral Reviews

ER -