| In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. | |
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MedLine Citation:
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PMID: 20828592 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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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Authors:
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Marta Kubera; Ewa Obuchowicz; Lisa Goehler; Joanna Brzeszcz; Michael Maes |
Publication Detail:
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Type: Journal Article Date: 2010-09-07 |
Journal Detail:
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Title: Progress in neuro-psychopharmacology & biological psychiatry Volume: 35 ISSN: 1878-4216 ISO Abbreviation: Prog. Neuropsychopharmacol. Biol. Psychiatry Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8211617 Medline TA: Prog Neuropsychopharmacol Biol Psychiatry Country: England |
Other Details:
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Languages: eng Pagination: 744-59 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Experimental Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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