Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.
Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.
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DOI：
10.1016/j.stemcr.2014.05.015
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发表时间：
2014-07-08
影响因子：
5.9
通讯作者：
Sawamoto, Kazunobu
中科院分区：
文献类型：
--
作者：
Zheng, Lian-Shun;Hitoshi, Seiji;Kaneko, Naoko;Takao, Keizo;Miyakawa, Tsuyoshi;Tanaka, Yasuhito;Xia, Hongjing;Kalinke, Ulrich;Kudo, Koutaro;Kanba, Shigenobu;Ikenaka, Kazuhiro;Sawamoto, Kazunobu
成年海马神经干细胞（NSCs）产生的新神经元在情绪调节和抗抑郁药物的作用中起重要作用。抑郁症是干扰素-α（IFN-α）的一种常见且严重的副作用，这限制了其作为抗病毒和抗肿瘤药物的应用。然而，IFN诱导的抑郁症的潜在机制在很大程度上是未知的。通过一系列综合的行为测试，我们发现接受IFN-α治疗的小鼠表现出抑郁样表型。IFN-α直接抑制NSC增殖，导致新神经元的产生减少。脑特异性IFN-α受体敲除小鼠可防止IFN-α诱导的抑郁行为表型和神经发生抑制，表明IFN-α抑制海马神经发生并通过其脑中的受体诱导抑郁。这些发现为理解IFN-α诱导的抑郁症的神经病理学基础和开发预防和治疗IFN-α诱导的抑郁症效应的新策略提供了见解。IFN-α处理的小鼠在一系列行为测试中表现出抑郁样表型IFN-α直接抑制成年海马中的NSC增殖IFN-α通过其脑中的受体抑制神经发生并诱导抑郁症抑郁症是干扰素-α（IFN-α）的常见且严重的副作用。然而，IFN诱导抑郁症的机制在很大程度上是未知的。在这里，Sawamoto，Kaneko及其同事证明，慢性IFN-α治疗导致抑郁样表型，并通过脑IFN受体直接抑制成年小鼠神经干细胞增殖。这些发现为了解干扰素诱导的抑郁症的神经病理学基础提供了新的见解。
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. IFN-α-treated mice show a depression-like phenotype in a behavioral test battery IFN-α directly suppresses NSC proliferation in adult hippocampus IFN-α suppresses neurogenesis and induced depression via its receptor in the brain Depression is a common and serious side effect of interferon-α (IFN-α). However, the mechanisms underlying IFN-induced depression are largely unknown. Here, Sawamoto, Kaneko, and colleagues demonstrate that chronic IFN-α treatment caused a depression-like phenotype and directly suppressed neural stem cell proliferation in adult mice via brain IFN receptor. These findings provide new insight for understanding the neuropathology underlying IFN-induced depression.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1017/s1461145708009516
发表时间：
2009-04-01
影响因子：
4.8
作者：
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