Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus

Naoko Kaneko, Koutaro Kudo, Tadashi Mabuchi, Keiko Takemoto, Koichiro Fujimaki, Henny Wati, Hironobu Iguchi, Hideo Tezuka, Shigenobu Kanba

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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.

Original languageEnglish
Pages (from-to)2619-2626
Number of pages8
JournalNeuropsychopharmacology
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 4 2006

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Kaneko, N., Kudo, K., Mabuchi, T., Takemoto, K., Fujimaki, K., Wati, H., ... Kanba, S. (2006). Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. Neuropsychopharmacology, 31(12), 2619-2626. https://doi.org/10.1038/sj.npp.1301137