The serum protein levels of the tPA–BDNF pathway are implicated in depression and antidepressant treatment
Open accessAbstract
Evidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA–BDNF pathway in MDD. We examined serum protein concentrations in the tPA–BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA–BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.
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Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain.
“Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain.”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [19]
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Self-citation
- Authors
- Jiang, H., Chen, S., Li, C., Lu, N., Yue, Y., Yin, Y., Zhang, Y., Zhi, X., Zhang, D., & Yuan, Y.
- Affiliations
- Zhongda Hospital Southeast University (CN)
- Nanjing University of Aeronautics and Astronautics (CN)
- Corresponding author
- Yuan, Y
- Venue
- Translational Psychiatry
- Published
- 2017-04-04
- Volume
- 7
- Issue
- 4
- Pages
- e1079-e1079
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC5416686
- OpenAlex
- W2604476397
- Cited by
- 148
- References
- 37
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 17 · 2023: 17 · 2022: 19 · 2021: 13 · 2020: 18 · 2019: 18 · 2018: 9 · 2017: 8
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81301167, 81371488, 81571330)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, depression, tissue plasminogen activator, brain-derived neurotrophic factor, proBDNF, TrkB, p75 neurotrophin receptor, antidepressant treatment, escitalopram, duloxetine, serum biomarkers, depression diagnosis
- MeSH terms
- Adult, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Nerve Tissue Proteins, Tissue Plasminogen Activator, Protein Kinases, Protein Precursors, Receptors, Nerve Growth Factor, Brain-Derived Neurotrophic Factor
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