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Cited by 443Tryptophan and brain disordersStress Responses and CortisolTreatment of Major Depression

The DOI matches its Crossref record; 215 of the 215 references it cites were found in a registry or an index.

In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression

Kubera, Marta, Obuchowicz, Ewa, Goehler, Lisa, Brzeszcz, Joanna, Maes, Michael·2011·Progress in Neuro-Psychopharmacology and Biological Psychiatry
DOI 10.1016/j.pnpbp.2010.08.026
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Abstract

Recently, the inflammatory and neurodegenerative (I&ND) hypothesis of depression was formulated (Maes et al., 2009), i.e. the neurodegeneration and reduced neurogenesis that characterize depression are caused by inflammation, cell-mediated immune activation and their long-term sequels. The aim of this paper is to review the body of evidence that external stressors may induce (neuro)inflammation, neurodegeneration and reduced neurogenesis; and that antidepressive treatments may impact on these pathways. The chronic mild stress (CMS) and learned helplessness (LH) models show that depression-like behaviors are accompanied by peripheral and central inflammation, neuronal cell damage, decreased neurogenesis and apoptosis in the hippocampus. External stress-induced depression-like behaviors are associated with a) increased interleukin-(IL)1β, tumor necrosis factor-α, IL-6, nuclear factor κB, cyclooxygenase-2, expression of Toll-like receptors and lipid peroxidation; b) antineurogenic effects and reduced brain-derived neurotrophic factor (BDNF) levels; and c) apoptosis with reduced levels of Bcl-2 and BAG1 (Bcl-2 associated athanogene 1), and increased levels of caspase-3. Stress-induced inflammation, e.g. increased IL-1β, but not reduced neurogenesis, is sufficient to cause depression. Antidepressants a) reduce peripheral and central inflammatory pathways by decreasing IL-1β, TNFα and IL-6 levels; b) stimulate neuronal differentiation, synaptic plasticity, axonal growth and regeneration through stimulatory effects on the expression of different neurotrophic factors, e.g. trkB, the receptor for brain-derived neurotrophic factor; and c) attenuate apoptotic pathways by activating Bcl-2 and Bcl-xl proteins, and suppressing caspase-3. It is concluded that external stressors may provoke depression-like behaviors through activation of inflammatory, oxidative, apoptotic and antineurogenic mechanisms. The clinical efficacity of antidepressants may be ascribed to their ability to reverse these different pathways.

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  1. Zunszain, 2010, Role of glucocorticoids and cytokines in neurodegenerative processes in depression, Progr Neuro-Psychopharmacol Biol Psychiatr

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Metadata

Authors
Kubera, M., Obuchowicz, E., Goehler, L., Brzeszcz, J., & Maes, M.
Affiliations
  • Maj Institute of Pharmacology (PL)
  • Medical University of Silesia (PL)
  • University of Virginia (US)
  • Oil and Gas Institute - National Research Institute (PL)
  • Piyavate Hospital (TH)
Corresponding author
Maes, Michael
ORCID
Venue
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher
Elsevier BV
Published
2011-04
Volume
35
Issue
3
Pages
744-759
ISSN
0278-5846 (ISSN-L)
DOI
10.1016/j.pnpbp.2010.08.026
OpenAlex
W2074349137
Cited by
443
References
215
Citations by year
2026: 14 · 2025: 18 · 2024: 29 · 2023: 24 · 2022: 27 · 2021: 42 · 2020: 36 · 2019: 24 · 2018: 31 · 2017: 30 · 2016: 30 · 2015: 25 · 2014: 29 · 2013: 30 · 2012: 37
FWCI
1.88
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
depression, neuroinflammation, neurodegeneration, apoptosis, chronic mild stress, learned helplessness, hippocampus, brain-derived neurotrophic factor, Bcl-2, caspase-3, IL-1β, TNF-α, interleukin-6, Toll-like receptors, antidepressants, oxidative stress, lipid peroxidation, neurotrophic factors, TrkB
MeSH terms
Animals, Depression, Disease Models, Animal, Female, Humans, Inflammation, Male, Stress, Psychological, Nitrosation, Oxidative Stress, Neurodegenerative Diseases, Neurogenesis

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