TY - JOUR
T1 - IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging
AU - Wakabayashi, Chisato
AU - Numakawa, Tadahiro
AU - Odaka, Haruki
AU - Ooshima, Yoshiko
AU - Kiyama, Yuji
AU - Manabe, Toshiya
AU - Kunugi, Hiroshi
AU - Iwakura, Yoichiro
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - Anxiety-like phenotype
KW - Elevated plus-maze test
KW - Glucocorticoid receptor
KW - Hippocampus
KW - IL-1 receptor antagonist
UR - http://www.scopus.com/inward/record.url?scp=84929615907&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2015.05.019
DO - 10.1016/j.neulet.2015.05.019
M3 - 記事
C2 - 26002078
AN - SCOPUS:84929615907
SN - 0304-3940
VL - 599
SP - 20
EP - 25
JO - Neuroscience Letters
JF - Neuroscience Letters
ER -