Abstract
The therapeutic use of interferon-alpha (IFN-α), a proinflammatory cytokine, is known to cause various neuropsychiatric adverse effects. In particular, depression occurs in 30–45% of patients, frequently interrupting treatment. IFN-α-treated animals also show depression-like behaviors. However, mechanisms underlying the depression caused by IFN-α remain to be defined. Recently, a decrease in adult hippocampal neurogenesis was revealed as a possible neuropathological mechanism of depression. Therefore, we investigated the effect of subchronic IFN-α treatment on neurogenesis in the adult rat dentate gyrus (DG). Immediately after the administration of IFN-α for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later. Also, an increase in the level of interleukin-1beta (IL-1β), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-α. Furthermore, coadministration of an IL-1 receptor antagonist completely blocked the IFN-α-induced suppression of the cell-proliferative activity in the DG. Our results indicate that IFN-α suppresses neurogenesis in the DG, and that IL-1β plays an essential role in the suppression. The decreased cell proliferation caused by IFN-α-induced IL-1β may be responsible, at least in part, for IFN-α-induced depression.
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Acknowledgements
This study was supported by the Target-Oriented Brain Science Promotion Program and a grant from the Ministry of Culture, Sports, and Science of Japan (#16390321). The study was also supported by grants from the Ministry of Health and Labor of Japan.
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Kaneko, N., Kudo, K., Mabuchi, T. et al. Suppression of Cell Proliferation by Interferon-Alpha through Interleukin-1 Production in Adult Rat Dentate Gyrus. Neuropsychopharmacol 31, 2619–2626 (2006). https://doi.org/10.1038/sj.npp.1301137
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DOI: https://doi.org/10.1038/sj.npp.1301137
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