Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.
dc.contributor.author | Zheng, Lian-Shun | |
dc.contributor.author | Hitoshi, Seiji | |
dc.contributor.author | Kaneko, Naoko | |
dc.contributor.author | Takao, Keizo | |
dc.contributor.author | Miyakawa, Tsuyoshi | |
dc.contributor.author | Tanaka, Yasuhito | |
dc.contributor.author | Xia, Hongjing | |
dc.contributor.author | Kalinke, Ulrich | |
dc.contributor.author | Kudo, Koutaro | |
dc.contributor.author | Kanba, Shigenobu | |
dc.contributor.author | Ikenaka, Kazuhiro | |
dc.contributor.author | Sawamoto, Kazunobu | |
dc.date.accessioned | 2014-11-05T14:42:34Z | en |
dc.date.available | 2014-11-05T14:42:34Z | en |
dc.date.issued | 2014-07-08 | en |
dc.identifier.citation | Mechanisms for interferon-α-induced depression and neural stem cell dysfunction. 2014, 3 (1):73-84 Stem Cell Reports | en |
dc.identifier.issn | 2213-6711 | en |
dc.identifier.pmid | 25068123 | en |
dc.identifier.doi | 10.1016/j.stemcr.2014.05.015 | en |
dc.identifier.uri | http://hdl.handle.net/10033/333729 | en |
dc.description.abstract | New neurons generated by the neural stem cells (NSCs) in the adult hippocampus play an important role in emotional regulation and respond to the action of antidepressants. Depression is a common and serious side effect of interferon-α (IFN-α), which limits its use as an antiviral and antitumor drug. However, the mechanism(s) underlying IFN-induced depression are largely unknown. Using a comprehensive battery of behavioral tests, we found that mice subjected to IFN-α treatment exhibited a depression-like phenotype. IFN-α directly suppressed NSC proliferation, resulting in the reduced generation of new neurons. Brain-specific mouse knockout of the IFN-α receptor prevented IFN-α-induced depressive behavioral phenotypes and the inhibition of neurogenesis, suggesting that IFN-α suppresses hippocampal neurogenesis and induces depression via its receptor in the brain. These findings provide insight for understanding the neuropathology underlying IFN-α-induced depression and for developing new strategies for the prevention and treatment of IFN-α-induced depressive effects. | |
dc.language.iso | en | en |
dc.title | Mechanisms for interferon-α-induced depression and neural stem cell dysfunction. | en |
dc.type | Article | en |
dc.contributor.department | Institute of Anatomy and Cell Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China ; Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan. | en |
dc.identifier.journal | Stem cell reports | en |
refterms.dateFOA | 2018-06-13T05:38:43Z | |
html.description.abstract | New neurons generated by the neural stem cells (NSCs) in the adult hippocampus play an important role in emotional regulation and respond to the action of antidepressants. Depression is a common and serious side effect of interferon-α (IFN-α), which limits its use as an antiviral and antitumor drug. However, the mechanism(s) underlying IFN-induced depression are largely unknown. Using a comprehensive battery of behavioral tests, we found that mice subjected to IFN-α treatment exhibited a depression-like phenotype. IFN-α directly suppressed NSC proliferation, resulting in the reduced generation of new neurons. Brain-specific mouse knockout of the IFN-α receptor prevented IFN-α-induced depressive behavioral phenotypes and the inhibition of neurogenesis, suggesting that IFN-α suppresses hippocampal neurogenesis and induces depression via its receptor in the brain. These findings provide insight for understanding the neuropathology underlying IFN-α-induced depression and for developing new strategies for the prevention and treatment of IFN-α-induced depressive effects. |