Cited by 58Nerve injury and regenerationTreatment of Major DepressionNeurotransmitter Receptor Influence on Behavior

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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Diniz, Cassiano R.A.F., Casarotto, Plinio C, Resstel, Leonardo, Joca, Sâmia R.L.·2018·Neuroscience & Biobehavioral Reviews

Abstract

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.

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Crossref · 10.1016/j.neubiorev.2018.04.001

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  • BDNF has been consistently associated with the therapeutic effect of antidepressant drugs.

    “BDNF has been consistently associated to the therapeutic effect of antidepressant drugs [199,200,201].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [201]

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Authors
Diniz, C. R. A. F., Casarotto, P. C., Resstel, L., & Joca, S. R. L.
Affiliations
  • Universidade de São Paulo (BR)
  • University of Helsinki (FI)
Corresponding author
Diniz, Cassiano R.A.F.
Venue
Neuroscience & Biobehavioral Reviews
Publisher
Elsevier BV
Published
2018-07
Volume
90
Pages
70-83
ISSN
0149-7634 (ISSN-L)
OpenAlex
W2795628695
Cited by
58
References
222
Citations by year
2026: 4 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 14 · 2019: 4 · 2018: 3
FWCI
1.00
Type
journal article
Language
en
Open access
Locations
  • Neuroscience & Biobehavioral Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação de Amparo à Pesquisa do Estado de São Paulo
  • European Research Council
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
brain-derived neurotrophic factor, proBDNF, antidepressant action, depression, post-traumatic stress disorder, TrkB signaling, p75 neurotrophin receptor, neuroplasticity, neuronal turnover, neuronal remodeling, stress response
MeSH terms
Antidepressive Agents, Brain, Depression, Neuronal Plasticity, Neurons, Brain-Derived Neurotrophic Factor

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