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Age-dependent regulation of depression-like behaviors through modulation of adrenergic receptor α₁A subtype expression revealed by the analysis of interleukin-1 receptor antagonist knockout mice.

Abstract：

:Interleukin-1 (IL-1) plays a crucial role in stress responses and its mRNA is induced in the brain by stress load; however, the precise role of IL-1 in higher brain functions and their abnormalities is largely unknown. Here, we report that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lack IL-1Ra molecules that antagonize the IL-1 receptor, displayed anti-depression-like phenotypes in the tail suspension test (TST) and forced-swim test (FST) only at a young stage (8 weeks), whereas the phenotypes disappeared at later stages (20 and 32 weeks). These anti-depression-like phenotypes were reversed by administration of adrenergic receptor (AR) antagonists against the ARα(1), ARα(2), and ARβ subtypes. Although the contents of 5-HT, norepinephrine (NE), and dopamine (DA), which are known to be associated with major symptoms of psychiatric disorders, were not significantly different in the hippocampus or cerebral cortex between IL-1Ra KO and their wild-type (WT) littermate mice, the mRNA expression level of the ARα(1A) subtype was significantly changed in the cerebral cortex. Interestingly, the change in expression of the ARα(1A) subtype was correlated with an age-dependent alteration in the TST and FST in IL-1Ra KO mice. Furthermore, mild immobilization stress loaded on C57BL/6J male mice caused similar anti-depression-like phenotypes in the TST and FST to those observed in mutant mice. These results suggest that sustained activation of IL-1 signaling induced by gene manipulation in mutant mice affects the expression of the ARα(1A) subtype and that modification of adrenergic signaling by the IL-1 system may ultimately cause significant psychiatric abnormalities such as depression, and this mutant mouse could be regarded as a model animal of depression that specifically appears in children and adolescents.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Wakabayashi C,Kiyama Y,Kunugi H,Manabe T,Iwakura Y

doi

10.1016/j.neuroscience.2011.06.031

subject

Has Abstract

pub_date

2011-09-29 00:00:00

pages

475-84

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(11)00715-9

journal_volume

192

pub_type

杂志文章

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Age-dependent regulation of depression-like behaviors through modulation of adrenergic receptor α₁A subtype expression revealed by the analysis of interleukin-1 receptor antagonist knockout mice.