IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging

Chisato Wakabayashi, Tadahiro Numakawa, Haruki Odaka, Yoshiko Ooshima, Yuji Kiyama, Toshiya Manabe, Hiroshi Kunugi, Yoichiro Iwakura

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus.

Original languageEnglish
Pages (from-to)20-25
Number of pages6
JournalNeuroscience Letters
Volume599
DOIs
StatePublished - 1 Jul 2015
Externally publishedYes

Keywords

  • Anxiety-like phenotype
  • Elevated plus-maze test
  • Glucocorticoid receptor
  • Hippocampus
  • IL-1 receptor antagonist

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