Analysis of Genes Linked to Depressive-like Behaviors in Interleukin-18-deficient Mice: Gene Expression Profiles in the Brain

Overview

Journal Biomed Rep

Specialty Biochemistry

Date 2019 Dec 17

PMID 31839943

Citations 5

Authors

Kyosuke Yamanishi

Takuya Hashimoto

Masahiro Miyauchi

Keiichiro Mukai

Kaoru Ikubo

Noriko Uwa

Yuko Watanabe

Takashi Ikawa

Daisuke Okuzaki

Haruki Okamura

Hiromichi Yamanishi

Hisato Matsunaga

Affiliations

Soon will be listed here.

Abstract

Interleukin (IL)-18 is an interferon γ-inducing inflammatory cytokine associated with function of the immune system and other physiological functions. IL-18-deficient ( ) 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 mice was analyzed to identify genes associated with the depressive-like behaviors and other impairments displayed by mice. Using whole genome microarray analysis, gene expression patterns in the brains of and 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 (); protein tyrosine phosphatase, non-receptor type 1 (); and urocortin 3 () 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 () and NADPH oxidase 4 (). The microarray analysis results were correlated with the results of reverse transcription-quantitative PCR (RT-qPCR). Overall, the results suggest that , and may be involved in depression-like changes and and regulate these three genes in IL-18-deficient mice.

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References

Takeda K, Tsutsui H, Yoshimoto T, Adachi O, Yoshida N, Kishimoto T . Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity. 1998; 8(3):383-90. DOI: 10.1016/s1074-7613(00)80543-9. View

Mahadev K, Motoshima H, Wu X, Ruddy J, Arnold R, Cheng G . The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. Mol Cell Biol. 2004; 24(5):1844-54. PMC: 350558. DOI: 10.1128/MCB.24.5.1844-1854.2004. View

Li C, Chen P, Vaughan J, Lee K, Vale W . Urocortin 3 regulates glucose-stimulated insulin secretion and energy homeostasis. Proc Natl Acad Sci U S A. 2007; 104(10):4206-11. PMC: 1820733. DOI: 10.1073/pnas.0611641104. View

Yamanishi K, Mukai K, Hashimoto T, Ikubo K, Nakasho K, El-Darawish Y . Physiological and molecular effects of interleukin-18 administration on the mouse kidney. J Transl Med. 2018; 16(1):51. PMC: 5842592. DOI: 10.1186/s12967-018-1426-6. View

Tochigi M, Iwamoto K, Bundo M, Sasaki T, Kato N, Kato T . Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains. Neurosci Res. 2007; 60(2):184-91. DOI: 10.1016/j.neures.2007.10.010. View

Yamanishi K, Doe N, Mukai K, Ikubo K, Hashimoto T, Uwa N . Interleukin-18-deficient mice develop hippocampal abnormalities related to possible depressive-like behaviors. Neuroscience. 2019; 408:147-160. DOI: 10.1016/j.neuroscience.2019.04.003. View

Okamura H, Tsutsi H, Komatsu T, Yutsudo M, HAKURA A, Tanimoto T . Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 1995; 378(6552):88-91. DOI: 10.1038/378088a0. View

Kasukawa T, Masumoto K, Nikaido I, Nagano M, Uno K, Tsujino K . Quantitative expression profile of distinct functional regions in the adult mouse brain. PLoS One. 2011; 6(8):e23228. PMC: 3155528. DOI: 10.1371/journal.pone.0023228. View

Ikubo K, Yamanishi K, Doe N, Hashimoto T, Sumida M, Watanabe Y . Molecular analysis of the mouse brain exposed to chronic mild stress: The influence of hepatocyte nuclear factor 4α on physiological homeostasis. Mol Med Rep. 2017; 16(1):301-309. DOI: 10.3892/mmr.2017.6577. View

10.

Kang H, Adams D, Simen A, Simen B, Rajkowska G, Stockmeier C . Gene expression profiling in postmortem prefrontal cortex of major depressive disorder. J Neurosci. 2007; 27(48):13329-40. PMC: 3763487. DOI: 10.1523/JNEUROSCI.4083-07.2007. View

11.

Yamanishi K, Doe N, Sumida M, Watanabe Y, Yoshida M, Yamamoto H . Hepatocyte nuclear factor 4 alpha is a key factor related to depression and physiological homeostasis in the mouse brain. PLoS One. 2015; 10(3):e0119021. PMC: 4361552. DOI: 10.1371/journal.pone.0119021. View

12.

Yoshida M, Watanabe Y, Yamanishi K, Yamashita A, Yamamoto H, Okuzaki D . Analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: gene expression profiles in the brain. Int J Mol Med. 2014; 33(4):887-96. DOI: 10.3892/ijmm.2014.1631. View

13.

Tezval H, Jahn O, Todorovic C, Sasse A, Eckart K, Spiess J . Cortagine, a specific agonist of corticotropin-releasing factor receptor subtype 1, is anxiogenic and antidepressive in the mouse model. Proc Natl Acad Sci U S A. 2004; 101(25):9468-73. PMC: 439000. DOI: 10.1073/pnas.0403159101. View

14.

Tsutsui H, Kayagaki N, Kuida K, Nakano H, Hayashi N, Takeda K . Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity. 1999; 11(3):359-67. DOI: 10.1016/s1074-7613(00)80111-9. View

15.

Hamilton J, Siemer M, Gotlib I . Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Mol Psychiatry. 2008; 13(11):993-1000. PMC: 2739676. DOI: 10.1038/mp.2008.57. View

16.

Yirmiya R, Weidenfeld J, Pollak Y, Morag M, Morag A, Avitsur R . Cytokines, "depression due to a general medical condition," and antidepressant drugs. Adv Exp Med Biol. 1999; 461:283-316. DOI: 10.1007/978-0-585-37970-8_16. View

17.

Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim E . A meta-analysis of cytokines in major depression. Biol Psychiatry. 2009; 67(5):446-57. DOI: 10.1016/j.biopsych.2009.09.033. View

18.

Fortress A, Schram S, Tuscher J, Frick K . Canonical Wnt signaling is necessary for object recognition memory consolidation. J Neurosci. 2013; 33(31):12619-26. PMC: 6618550. DOI: 10.1523/JNEUROSCI.0659-13.2013. View

19.

Liu H, Luiten P, Eisel U, DeJongste M, Schoemaker R . Depression after myocardial infarction: TNF-α-induced alterations of the blood-brain barrier and its putative therapeutic implications. Neurosci Biobehav Rev. 2013; 37(4):561-72. DOI: 10.1016/j.neubiorev.2013.02.004. View

20.

Yamanishi K, Maeda S, Kuwahara-Otani S, Hashimoto T, Ikubo K, Mukai K . Deficiency in interleukin-18 promotes differentiation of brown adipose tissue resulting in fat accumulation despite dyslipidemia. J Transl Med. 2018; 16(1):314. PMC: 6245626. DOI: 10.1186/s12967-018-1684-3. View