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| Content Provider | PubMed Central |
|---|---|
| Author | Zheng, Lian-shun Kaneko, Naoko Sawamoto, Kazunobu |
| Copyright Year | 2015 |
| Abstract | Interferon-alpha (IFN-α) is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs) in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for 5 weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments. |
| Related Links | http://dx.doi.org/10.3389/fncel.2015.00005 |
| Starting Page | 5 |
| File Format | |
| ISSN | 16625102 |
| e-ISSN | 16625102 |
| Journal | Frontiers in Cellular Neuroscience |
| Volume Number | 9 |
| Language | English |
| Publisher | Frontiers Media S.A. |
| Publisher Date | 2015-01-01 |
| Access Restriction | Open |
| Rights Holder | Frontiers Media S.A. |
| Subject Keyword | Cellular and Molecular Neuroscience Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cellular and Molecular Neuroscience |
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