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| Content Provider | Springer Nature Link |
|---|---|
| Author | Hoyo Becerra, Carolina Liu, Zijian Yao, Jinghong Kaltwasser, Britta Gerken, Guido Hermann, Dirk M. Schlaak, Joerg F. |
| Copyright Year | 2014 |
| Abstract | Major depression is a serious side effect of interferon-α (IFN-α), which is used in the therapy of hepatitis C virus (HCV) infection. Due to the lack of reproducible animal models, the mechanisms underlying IFN-α-related depression are largely unknown. We herein established a mouse model, in which murine IFN-α (250 IU/day) and polyinosinic/polycytidylic acid (poly(I:C); 1 μg/day), a toll-like receptor-3 (TLR3) agonist that mimics the effect of HCV double-strand RNA, were continuously infused into the lateral ventricle via miniosmotic pumps over up to 14 days. The delivery of IFN-α and poly(I:C), but not of IFN-α or poly(I:C) alone, resulted in a reproducible depression-like state that was characterized by reduced exploration behavior in open-field tests, increased immobility in tail suspension and forced swimming tests, and a moderate loss of body weight. In the hippocampus and prefrontal cortex, the pro-inflammatory genes TNF-α, IL-6, tissue inhibitor of metalloproteinases-1 (Timp-1), CXC motif ligand-1 (Cxcl1), Cxcl10, and CC motif ligand-5 (Ccl5) were synergistically induced by IFN-α and poly(I:C), most pronounced after 14-day exposure. In comparison, the interferon-inducible genes of signal transducer and activator of transcription-1 (Stat1), guanylate binding protein-1 (Gbp1), proteasome subunit-β type-9 (Psmb9), ubiquitin-conjugating enzyme E2L-6 (Ube2l6), receptor transporter protein-4 (Rtp4), and GTP cyclohydrolase-1 (Gch1), which had previously been elevated in the blood of IFN-α-treated patients developing depression, in the brains of suicidal individuals, and in primary neurons exposed to IFN-α and poly(I:C), were induced even earlier, reaching maximum levels mostly after 24 hours. We propose that interferon-inducible genes might be useful markers of imminent depression. |
| Starting Page | 318 |
| Ending Page | 329 |
| Page Count | 12 |
| File Format | |
| ISSN | 08937648 |
| Journal | Molecular Neurobiology |
| Volume Number | 52 |
| Issue Number | 1 |
| e-ISSN | 15591182 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2014-08-27 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Depression Interferon-α TLR3 activation Interferon-inducible genes Cytokines Neurosciences Neurobiology Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Cellular and Molecular Neuroscience |
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