Interleukin (IL)-18 is an
interferon γ-inducing inflammatory
cytokine associated with function of the immune system and other physiological functions. IL-18-deficient (
Il18 -/-) mice exhibit
obesity,
dyslipidemia, non-
alcoholic steatohepatitis and depressive-like behavioral changes. Therefore,
IL-18 has a number of important roles associated with immunity, energy homeostasis and psychiatric conditions. In the present study, gene expression in the brains of
Il18 -/- mice was analyzed to identify genes associated with the depressive-like behaviors and other impairments displayed by
Il18 -/- mice. Using whole genome microarray analysis, gene expression patterns in the brains of
Il18 +/+ and
Il18 -/- mice at 6 and 12 weeks of age were examined and compared. Subsequently, genes were categorized using Ingenuity® Pathway Analysis (IPA). At 12 weeks of age, 2,805 genes were identified using microarray analysis. Genes related to 'Major depression' and '
Depressive disorders' were identified by IPA core analysis, and 13 genes associated with depression were isolated. Among these genes,
fibroblast growth factor receptor 1 (
Fgfr1); protein tyrosine phosphatase, non-receptor type 1 (Ptpn1); and
urocortin 3 (Ucn3) were classed as depression-inducing and the other genes were considered depression-suppressing genes. Subsequently, the interactions between the microarray results at 6 weeks of age and the above three depression-inducing genes were analyzed to search for effector genes of depression at 12 weeks of age. This analysis identified
cyclin D1 (Ccnd1) and
NADPH oxidase 4 (Nox4). The microarray analysis results were correlated with the results of reverse transcription-quantitative PCR (RT-qPCR). Overall, the results suggest that Fgfr1, Ptpn1 and Ucn3 may be involved in depression-like changes and Ccnd1 and Nox4 regulate these three genes in IL-18-deficient mice.