title: Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.
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.
authors: 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.
authors: Lian-Shun
authors: LS
authors: Zheng
authors: 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.
authors: Seiji
authors: S
authors: Hitoshi
authors: Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors: Naoko
authors: N
authors: Kaneko
authors: 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.
authors: Keizo
authors: K
authors: Takao
authors: 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.
authors: Tsuyoshi
authors: T
authors: Miyakawa
authors: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors: Yasuhito
authors: Y
authors: Tanaka
authors: Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors: Hongjing
authors: H
authors: Xia
authors: 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.
authors: Ulrich
authors: U
authors: Kalinke
authors: Yokohama Clinic, Yokohama, Kanagawa 220-0004, Japan.
authors: Koutaro
authors: K
authors: Kudo
authors: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors: Shigenobu
authors: S
authors: Kanba
authors: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
authors: Kazuhiro
authors: K
authors: Ikenaka
authors: Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors: Kazunobu
authors: K
authors: Sawamoto
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003863:Depression / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology*
chemical_list: D016898:Interferon-alpha