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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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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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“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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Metadata
- 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
- Semantic Scholar
- 901c33994c7064d67a1d28eaac7aa0969a073d89
- 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
- green
- hdl.handle.net
- 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 (medical) › 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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