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Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.
Zheng, Lian-Shun Hitoshi, Seiji Kaneko, Naoko Takao, Keizo Miyakawa, Tsuyoshi Tanaka, Yasuhito Xia, Hongjing Kalinke, Ulrich Kudo, Koutaro Kanba, Shigenobu
Zheng, Lian-Shun
Hitoshi, Seiji
Kaneko, Naoko
Takao, Keizo
Miyakawa, Tsuyoshi
Tanaka, Yasuhito
Xia, Hongjing
Kalinke, Ulrich
Kudo, Koutaro
Kanba, Shigenobu
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2014-07-08
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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.
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Mechanisms for interferon-α-induced depression and neural stem cell dysfunction. 2014, 3 (1):73-84 Stem Cell Reports
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en
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2213-6711