Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice.
Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice.
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DOI：
10.1016/j.nbd.2012.08.020
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发表时间：
2013-01
影响因子：
6.1
通讯作者：
Hagg T
中科院分区：
文献类型：
--
作者：
Kang SS;Keasey MP;Arnold SA;Reid R;Geralds J;Hagg T
成年大鼠局灶性脑缺血可迅速且强烈地诱导室下区（SVZ）的神经发生，但在小鼠中的相关报道较少且不一致，这对从基因层面研究如睫状神经营养因子（CNTF）等内源性神经发生调节因子构成了障碍。在此，我们首先通过研究表明，成年雄性C57BL/6小鼠大脑中动脉闭塞（MCAO）仅在非常特定的条件下，即闭塞30分钟后14天，可强烈促进室下区的神经发生，从而为进一步研究提供了一个平台。CNTF的表达与增殖的、BrdU阳性的室下区细胞数量的变化平行。在CNTF - / -小鼠中不存在中风诱导的增殖，这表明它是由CNTF介导的。MCAO增加的CNTF似乎作用于C细胞增殖，并通过诱导成纤维细胞生长因子2（FGF2）的表达，但不是通过室下区神经干细胞的表皮生长因子（EGF）表达或Notch1信号传导。CNTF是独特的，因为其他gp130配体白细胞介素 - 6（IL - 6）和白血病抑制因子（LIF）的表达不能预测室下区增殖，或者在CNTF - / -小鼠中没有或仅有很小的代偿性增加。肿瘤坏死因子 - α的表达可抑制神经发生，其在室下区的表达以及白细胞的存在与神经发生呈负相关，但促炎细胞因子不影响培养的星形胶质细胞中CNTF的表达。这些结果表明，室下区缓慢上调的CNTF介导中风诱导的神经发生，并被炎症所抵消。进一步对内源性CNTF进行药物刺激可能是中风后细胞替代的一种良好治疗策略，因为CNTF调节正常的神经发生模式，且几乎仅在神经系统中表达。
Focal brain ischemia in adult rats rapidly and robustly induces neurogenesis in the subventricular zone (SVZ) but there are few and inconsistent reports in mice, presenting a hurdle to genetically investigate the endogenous neurogenic regulators such as ciliary neurotrophic factor (CNTF). Here, we first provide a platform for further studies by showing that middle cerebral artery occlusion in adult male C57BL/6 mice robustly enhances neurogenesis in the SVZ only under very specific conditions, i.e., 14 days after a 30 min occlusion. CNTF expression paralleled changes in the number of proliferated, BrdU-positive, SVZ cells. Stroke-induced proliferation was absent in CNTF−/− mice, suggesting that it is mediated by CNTF. MCAO-increased CNTF appears to act on C cell proliferation and by inducing FGF2 expression but not via EGF expression or Notch1 signaling of neural stem cells in the SVZ. CNTF is unique, as expression of other gp130 ligands, IL-6 and LIF, did not predict SVZ proliferation or showed no or only small compensatory increases in CNTF−/− mice. Expression of tumor necrosis factor-α, which can inhibit neurogenesis, and the presence of leukocytes in the SVZ were inversely correlated with neurogenesis, but pro-inflammatory cytokines did not affect CNTF expression in cultured astrocytes. These results suggest that slowly up-regulated CNTF in the SVZ mediates stroke-induced neurogenesis and is counteracted by inflammation. Further pharmacological stimulation of endogenous CNTF might be a good therapeutic strategy for cell replacement after stroke as CNTF regulates normal patterns of neurogenesis and is expressed almost exclusively in the nervous system.
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影响因子：
6.1
作者：
Kernie SG;Parent JM
通讯作者：
Parent JM
影响因子：
5.3
作者：
Iosif, Robert E.;Ekdahl, Christine T.;Lindvall, Olle
通讯作者：
Lindvall, Olle
DOI：
10.1097/00004647-200404000-00005
发表时间：
2004-04-01
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：
Bernaudin, Myriam
DOI：
10.1073/pnas.0603512103
发表时间：
2006-08-29
影响因子：
11.1
作者：
Jin, Kunlin;Wang, Xiaomei;Greenberg, David A.
通讯作者：
Greenberg, David A.