2.50
Hdl Handle:
http://hdl.handle.net/10033/333729
Title:
Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.
Authors:
Zheng, Lian-Shun; Hitoshi, Seiji; Kaneko, Naoko; Takao, Keizo; Miyakawa, Tsuyoshi; Tanaka, Yasuhito; Xia, Hongjing; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Kudo, Koutaro; Kanba, Shigenobu; Ikenaka, Kazuhiro; Sawamoto, Kazunobu
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.
Affiliation:
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.
Citation:
Mechanisms for interferon-α-induced depression and neural stem cell dysfunction. 2014, 3 (1):73-84 Stem Cell Reports
Journal:
Stem cell reports
Issue Date:
8-Jul-2014
URI:
http://hdl.handle.net/10033/333729
DOI:
10.1016/j.stemcr.2014.05.015
PubMed ID:
25068123
Type:
Article
Language:
en
ISSN:
2213-6711
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorZheng, Lian-Shunen
dc.contributor.authorHitoshi, Seijien
dc.contributor.authorKaneko, Naokoen
dc.contributor.authorTakao, Keizoen
dc.contributor.authorMiyakawa, Tsuyoshien
dc.contributor.authorTanaka, Yasuhitoen
dc.contributor.authorXia, Hongjingen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorKudo, Koutaroen
dc.contributor.authorKanba, Shigenobuen
dc.contributor.authorIkenaka, Kazuhiroen
dc.contributor.authorSawamoto, Kazunobuen
dc.date.accessioned2014-11-05T14:42:34Zen
dc.date.available2014-11-05T14:42:34Zen
dc.date.issued2014-07-08en
dc.identifier.citationMechanisms for interferon-α-induced depression and neural stem cell dysfunction. 2014, 3 (1):73-84 Stem Cell Reportsen
dc.identifier.issn2213-6711en
dc.identifier.pmid25068123en
dc.identifier.doi10.1016/j.stemcr.2014.05.015en
dc.identifier.urihttp://hdl.handle.net/10033/333729en
dc.description.abstractNew 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.en
dc.language.isoenen
dc.titleMechanisms for interferon-α-induced depression and neural stem cell dysfunction.en
dc.typeArticleen
dc.contributor.departmentInstitute 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.journalStem cell reportsen

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