IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging. (10th July 2015)

• Record Type: Journal Article
• Authors: Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro
• Is Part Of: Neuroscience letters. Volume 599(2015)
• Page Start: 20
• Page End: 25
• Publication Date: 2015-07-10
• Subjects: ANOVA analysis of variance -- DA dopamine -- DOPAC 3, 4-dihydroxyphenylacetic acid -- EDTA ethylenediaminetetraacetic acid -- EPM elevated plus-maze -- GABA γ-amino-butyric acid -- GHB γ-hydroxybutyrate -- GR glucocorticoid receptor -- 5-HIAA 5-hydroxyindole acetic acid -- HPA hypothalamic-pituitary-adrenal -- HPLC high-performance liquid chromatography -- 5-HT 5-hydroxytryptamine -- HVA homovanillic acid -- IL-1 interleukin-1 -- IL-1Ra interleukin-1 receptor antagonist -- KO knockout -- MR mineralocorticoid receptor -- SDS sodium dodecylsulfate -- WT wild-type; Anxiety-like phenotype -- Elevated plus-maze test -- Glucocorticoid receptor -- Hippocampus -- IL-1 receptor antagonist; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2015.05.019
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: IL-1Ra KO mice showed anxiety-like phenotype in the EPM test at 20 weeks old. Anxiety-like phenotype was improved by the administration of diazepam. GR expression was decreased in IL-1Ra KO hippocampus at 20 weeks old. Tryptophan, 5-HIAA and HVA were increased in 20-week-old IL-1Ra KO mice. 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.