Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches

Dantzer, Robert

doi:10.1007/7854_2016_6

Cited by 248Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches

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Dantzer, Robert·2016·Current topics in behavioral neurosciences

DOI 10.1007/7854_2016_6PMC PMC6585430

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Abstract

Physically ill patients with chronic inflammation often present with symptoms of depression. Our understanding of the pathophysiology of inflammation-associated depression has benefited from preclinical studies on the mechanisms of sickness and clinical studies on the symptoms of sickness and depression that develop in patients treated with immunotherapy. Sickness behavior develops when the immune system is activated by pathogen- or damage-associated molecular patterns. It is a normal biological response to infection and cell injury. It helps the organism to mobilize its immune and metabolic defenses to fight the danger. Depression emerges on the background of sickness when the inflammatory response is too intense and long lasting or the resolution process is deficient. The transition from sickness to depression is mediated by activation of the kynurenine metabolism pathway that leads to the formation of neurotoxic kynurenine metabolites including quinolinic acid, an agonist of N-methyl-D-aspartate receptors. The neuroimmune processes and molecular factors that have been identified in the studies of inflammation-associated depression represent potential new targets for the development of innovative therapies for the treatment of major depressive disorders.

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There are links between inflammation-induced activation of IDO, the kynurenine metabolism pathway, and depression.
“Another review by Danzer et al. suggests links between the inflammation-induced activation of indolamine 2,3-dioxegenase (the enzyme that converts tryptophan to kynurenine), the kynurenine metabolism pathway, and depression”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [184]
The kynurenine pathway has been implicated in general depressed mood (inflammation-induced depression) and postpartum depression.
“The kynurenine pathway has been implicated not only in general depressed mood (inflammation-induced depression) [184,214,219] but also postpartum depression [120].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [184]

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Dynamic changes in metabolites of the kynurenine pathway in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease: A systematic Review and meta-analysis
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Kuwano, N., Kato, T. A., Setoyama, D., Sato-Kasai, M., Shimokawa, N., Hayakawa, K., Ohgidani, M., Sagata, N., Kubo, H., Kishimoto, J., et al. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.01.014 · Cited by 69 · see citing works
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Kynurenine metabolism and inflammation-induced depressed mood: a human experimental study
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Resistance Exercise Reduces Kynurenine Pathway Metabolites in Breast Cancer Patients Undergoing Radiotherapy
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IDO/Kynurenine; novel insight for treatment of inflammatory diseases
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Calpain inhibition ameliorates depression-like behaviors by reducing inflammation and promoting synaptic protein expression in the hippocampus
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Hericium Erinaceus Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells
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PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers
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Inflammatory Pathways in Psychiatric Disorders: the Case of Schizophrenia and Depression
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Memantine treatment exerts an antidepressant-like effect by preventing hippocampal mitochondrial dysfunction and memory impairment via upregulation of CREB/BDNF signaling in the rat model of chronic unpredictable stress-induced depression
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Bioenergetics and synaptic plasticity as potential targets for individualizing treatment for depression
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Emerging biotechnologies for evaluating disruption of stress, sleep, and circadian rhythm mechanism using aptamer-based detection of salivary biomarkers
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Omics approaches open new horizons in major depressive disorder: from biomarkers to precision medicine
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The role of immunomodulators in treatment-resistant depression: case studies
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Authors: Dantzer, R.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Dantzer, Robert
ORCID: Dantzer, Robert
Venue: Current topics in behavioral neurosciences
Publisher: Springer International Publishing
Published: 2016
Volume: 31
Pages: 117-138
ISSN: 1866-3370 (ISSN-L)
1866-3389
DOI: 10.1007/7854_2016_6
PMC: PMC6585430
OpenAlex: W2396821322
Cited by: 248
References: 92
Citations by year: 2026: 19 · 2025: 17 · 2024: 28 · 2023: 19 · 2022: 35 · 2021: 35 · 2020: 44 · 2019: 17 · 2018: 22 · 2017: 9 · 2016: 3
FWCI: 3.72
Type: book chapter
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (unspecified)
Locations: Current topics in behavioral neurosciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R21MH104694)
National Cancer Institute (R01CA193522, R21CA183736, P30CA016672)
National Institute of Neurological Disorders and Stroke (R01NS074999, R01NS073939)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: sickness behavior, chronic inflammation, quinolinic acid, neuroinflammation, major depressive disorder, immunotherapy, preclinical models
MeSH terms: Animals, Depressive Disorder, Humans, Inflammation, Kynurenine, Neuroimmunomodulation, Metabolic Networks and Pathways

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Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches

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