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
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“There is particular interest in how inflammatory cell types in the brain cause depressive symptoms, as anti-inflammatory treatments reduce depressive symptoms in humans [173] and chronic stress enhances inflammation in animal models [174].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [174]
Citations
Cites
Items 201–215 of 215
Kubera, M., Basta‐Kaim, A., Budziszewska, B., et al. (2005) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145705005663 · Cited by 28
Self-citationExpression and selective inhibition of constitutive and inducible forms of cyclooxygenase.
Seibert, K., Masferrer, J., Zhang, Y., et al. (1995) · PubMed · Cited by 25
Bonaccorso, S., Maier, S. F., Meltzer, H. Y., & Maes, M. H. J. (2002) · Journal of Affective Disorders · doi:10.1016/s0165-0327(02)00118-0 · Cited by 23
Self-citationPedreáñez, A. B., Arcaya, J. L., Carrizo, E., & Mosquera, J. (2006) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2006.07.018 · Cited by 23
Endotoxin inhibitor blocks heat exposure-induced expression of brain cytokine mRNA in aged rats
Katafuchi, T., Takaki, A., Take, S., Kondo, T., & Yoshimura, M. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(03)00331-0 · Cited by 22
GSK-3β : une kinase au cœur des maladies neuro-dégénératives ?
Petit-Paitel, A. (2010) · médecine/sciences · doi:10.1051/medsci/2010265516 · Cited by 22
Luckman, S. M., & Bicknell, R. J. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90919-k · Cited by 21
Psychological stress, cytokines and the inflammatory response system
Maes, M. H. J. (1999) · Current Opinion in Psychiatry · doi:10.1097/00001504-199911000-00019 · Cited by 21
Self-citationPsychological stress and the inflammatory response system
Maes, M. H. J. (2001) · Clinical Science · doi:10.1042/cs20010157 · Cited by 17
Self-citationThe effect of chronic mild stress on tumor-bearing rats’ behavior and its mechanism
Xiu, L., Lin, H., & Wei, P.-K. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.06.031 · Cited by 16
Williams, M. A., Turchan, J. T., Yang, L., et al. (2005) · Experimental Brain Research · doi:10.1007/s00221-005-2307-9 · Cited by 15
Wang, S., Zhang, Z., Guo, Y., Sui, Y., & Sun, Y. (2010) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e328334b677 · Cited by 15
Kubera, M., Roman, A., Basta‐Kaim, A., Budziszewska, B., Zajı́cová, A., Holáň, V., Rogóż, Z., Skuza, G., Leśkiewicz, M., Regulska, M., et al. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.11.017 · Cited by 13
Self-citationStress-induced changes of interleukin-1beta within the limbic system in the rat.
Badowska‐Szalewska, E., Klejbor, I., Sidor-Kaczmarek, J., Cecot, T., Lietzau, G., Spodnik, J. H., & Moryś, J. (2009) · PubMed · Cited by 8
Guo, Y., Zhang, Z., Wang, S., et al. (2008) · PubMed · Cited by 2
Flagged first, then by citations
Research works printed but not linked: 1
- Zunszain, 2010, Role of glucocorticoids and cytokines in neurodegenerative processes in depression, Progr Neuro-Psychopharmacol Biol Psychiatr
Cited by
Sorted by citations
So depression is an inflammatory disease, but where does the inflammation come from?
Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., Allen, N. B., Stuart, A. L., Hayley, A. C., Byrne, M. L., et al. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-200 · Cited by 1,423
Self-citationLeonard, B., & Maes, M. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.12.005 · Cited by 805
Self-citationDepression and sickness behavior are Janus-faced responses to shared inflammatory pathways
Maes, M., Berk, M., Goehler, L., Song, C., Anderson, G., Gałecki, P., & Leonard, B. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-66 · Cited by 629
Self-citationPathogenesis of depression: Insights from human and rodent studies
Ménard, C., Hodes, G. E., & Russo, S. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.053 · Cited by 593
Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity
Calabrese, F., Rossetti, A. C., Racagni, G., Gass, P., Riva, M. A., & Molteni, R. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00430 · Cited by 482
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
- 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)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
