The DOI matches its Crossref record; 76 of the 77 references it cites were found in a registry or an index.
Interleukin-1β: A New Regulator of the Kynurenine Pathway Affecting Human Hippocampal Neurogenesis
Open accessAbstract
Increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. Here, we show for the first time how IL-1β, a pro-inflammatory cytokine shown to be increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. IL-1β was detrimental to neurogenesis, as shown by a decrease in the number of doublecortin-positive neuroblasts (-28%), and mature, microtubule-associated protein-2-positive neurons (-36%). Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1β induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), kynurenine 3-monooxygenase (KMO), and kynureninase (42-, 12- and 30-fold increase, respectively, under differentiating conditions), the enzymes involved in the neurotoxic arm of the kynurenine pathway. Moreover, treatment with IL-1β resulted in an increase in kynurenine, the catabolic product of IDO-induced tryptophan metabolism. Interestingly, co-treatment with the KMO inhibitor Ro 61-8048 reversed the detrimental effects of IL-1β on neurogenesis. These observations indicate that IL-1β has a critical role in regulating neurogenesis whereas affecting the availability of tryptophan and the production of enzymes conducive to toxic metabolites. Our results suggest that inhibition of the kynurenine pathway may provide a new therapy to revert inflammatory-induced reduction in neurogenesis.
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“In preclinical models, activation of inflammation using LPS increases the activity of IDO thereby allocating more tryptophan metabolism toward the kynurenine pathway rather than serotonin synthesis (Zunszain et al., 2012), ultimately resulting in serotonin deficiency (See Dantzer et al., 2011; Nikkheslat et al., 2018; O’Farrell and Harkin, 2017 for a review of research on the kynurenine pathway).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Zunszain et al., 2012
In the citing paper
“Similarly, blood testing has identified genes (e.g., NRG1 which is involved in regulation of proliferation, survival, and differentiation of many cell types including neurons and epithelial cells207), proteins (e.g. CD47 which is implicated in neuroinflammatory cascades208), and proinflammatory markers (IL-1β, IL-6)209-211 that are associated with depression.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [210]
In the citing paper
“an effect that is mediated by an increased production of neurotoxic tryptophan metabolites as well as an increased oxidative stress”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Zunszain et al., 2012
In the citing paper
“we found that two proinflammatory cytokines, IL-1 and interferon-alpha, reduce human neurogenesis and human neuronal survival”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Zunszain et al., 2012
In the citing paper
“We also showed that the detrimental effects of these inflammatory stimuli can be reversed by antidepressant treatments as diverse as inhibitors of the kynurenine pathways, antioxidants and mitochondrial modulators, and omega-3 polyunsaturated fatty acids”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Zunszain et al., 2012
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Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
The Ki-67 protein: From the known and the unknown
Scholzen, T. E., & Gerdes, J. (2000) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(200003)182:3 · Cited by 4,707
Biologic basis for interleukin-1 in disease.
Dinarello, C. (1996) · Blood · doi:10.1182/blood.v87.6.2095.bloodjournal8762095 · Cited by 4,344
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766
Inflammatory Blockade Restores Adult Hippocampal Neurogenesis
Monje, M. L., Toda, H., & Palmer, T. D. (2003) · Science · doi:10.1126/science.1088417 · Cited by 2,426
ADULT NEUROGENESIS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM
Ming, G., & Song, H. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.051804.101459 · Cited by 1,891
Inflammation is detrimental for neurogenesis in adult brain
Ekdahl, C. T., Claasen, J.-H., Bonde, S., Kokaia, Z., & Lindvall, O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2234031100 · Cited by 1,559
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Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530
Neuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107
Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.67 · Cited by 1,084
Self-citationThe kynurenine pathway: a finger in every pie
Savitz, J. B. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0414-4 · Cited by 805
Mental health and HIV/AIDS: the need for an integrated response
Remien, R. H., Stirratt, M. J., Nguyen, N., Robbins, R. N., Pala, A. N., & Mellins, C. A. (2019) · AIDS · doi:10.1097/qad.0000000000002227 · Cited by 727
Metadata
- Authors
- Zunszain, P. A., Anacker, C., Cattaneo, A., Choudhury, S., Musaelyan, K., Myint, A. M., Thuret, S., Price, J., & Pariante, C. M.
- Affiliations
- King's College London (GB)
- University of Brescia (IT)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Pariante, Carmine M
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2011-11-09
- Volume
- 37
- Issue
- 4
- Pages
- 939-949
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3280640
- OpenAlex
- W2128944765
- Cited by
- 388
- References
- 77
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 20 · 2023: 19 · 2022: 27 · 2021: 36 · 2020: 33 · 2019: 30 · 2018: 23 · 2017: 27 · 2016: 29 · 2015: 33 · 2014: 35 · 2013: 22 · 2012: 17
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Funders
- South London and Maudsley NHS Foundation Trust
- National Alliance for Research on Schizophrenia and Depression
- National Institute for Health and Care Research
- Research Councils UK
- Medical Research Council (MR/J002739/1)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- IL-1β, kynurenine pathway, hippocampal neurogenesis, neurogenesis, major depressive disorder, inflammation, indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase, kynureninase, tryptophan metabolism, neurotoxic metabolites, hippocampal progenitor cells
- MeSH terms
- Cell Differentiation, Cell Line, Hippocampus, Humans, Inflammation, Kynurenine, Neural Inhibition, Signal Transduction, Multipotent Stem Cells, Interleukin-1beta, Neurogenesis
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