The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression
Open accessAbstract
Pain and depression are frequently comorbid disorders, but the mechanism underlying this association is unknown. Here, we report that brain indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in this comorbidity. We found that chronic pain in rats induced depressive behavior and IDO1 upregulation in the bilateral hippocampus. Upregulation of IDO1 resulted in the increased kynurenine/tryptophan ratio and decreased serotonin/tryptophan ratio in the bilateral hippocampus. We observed elevated plasma IDO activity in patients with both pain and depression, as well as in rats with anhedonia induced by chronic social stress. Intra-hippocampal administration of IL-6 in rats, in addition to in vitro experiments, demonstrated that IL-6 induces IDO1 expression through the JAK/STAT pathway. Further, either Ido1 gene knockout or pharmacological inhibition of hippocampal IDO1 activity attenuated both nociceptive and depressive behavior. These results reveal an IDO1-mediated regulatory mechanism underlying the comorbidity of pain and depression and suggest a new strategy for the concurrent treatment of both conditions via modulation of brain IDO1 activity.
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Indoleamine 2,3 dioxygenase and metabolic control of immune responses
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The kynurenine pathway: a finger in every pie
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Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation
Minhas, P. S., Liu, L., Moon, P. K., Joshi, A. U., Dove, C., Mhatre, S., Contrepois, K., Wang, Q., Lee, B. A., Coronado, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0255-3 · Cited by 501
Neuroinflammation and comorbidity of pain and depression
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Microbiota alteration is associated with the development of stress-induced despair behavior
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Metadata
- Authors
- Kim, H., Chen, L., Lim, G., Sung, B., Wang, S., McCabe, M. F., Rusanescu, G., Yang, L., Tian, Y., & Mao, J.
- Venue
- Journal of Clinical Investigation
- Published
- 2012-08-01
- Volume
- 122
- Issue
- 8
- Pages
- 2940-2954
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2088936071
- Cited by
- 324
- References
- 80
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- green
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