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Stem Cell Reports. 2014 Jun 26;3(1):73-84. doi: 10.1016/j.stemcr.2014.05.015. eCollection 2014 Jul 8.

Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.

Author information

1
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.
2
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan ; Department of Integrative Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
3
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
4
Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan ; Japan Science and Technology Agency, Core Research for Evolutionary Science and Technology (CREST), Kawaguchi 332-0012, Japan.
5
Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan ; Japan Science and Technology Agency, Core Research for Evolutionary Science and Technology (CREST), Kawaguchi 332-0012, Japan ; Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake 470-1192, Japan.
6
Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
7
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover 30625, Germany.
8
Yokohama Clinic, Yokohama, Kanagawa 220-0004, Japan.
9
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
10
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.

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.

PMID:
25068123
PMCID:
PMC4110771
DOI:
10.1016/j.stemcr.2014.05.015
[Indexed for MEDLINE]
Free PMC Article

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