The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain.
The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain.
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DOI：
10.1111/j.1471-4159.2009.06212.x
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发表时间：
2009-08
影响因子：
4.7
通讯作者：
Chuang DM
中科院分区：
文献类型：
--
作者：
Kim HJ;Leeds P;Chuang DM
在健康成人脑中，神经发生通常发生在脑室下区（SVZ）和海马齿状回（DG）。脑缺血增强成年啮齿类动物缺血脑神经源性和非神经源性区域的神经发生。本研究表明，损伤后用HDAC抑制剂丁酸钠（SB）治疗，刺激溴-2 ′-脱氧尿苷（BrdU）在SVZ，DG，纹状体和额叶皮质在缺血脑的大鼠永久性脑缺血。SB治疗还增加了脑缺血后不同脑区表达聚唾液酸-神经细胞粘附分子（PSA-NCAM）、巢蛋白、GFAP、磷酸化CREB和脑源性神经营养因子（BDNF）的细胞数量。此外，广泛的共定位的BrdU和PSA-NCAM观察到在多个区域缺血后，SB治疗上调BDNF，磷酸化CREB和GFAP的蛋白水平。脑室内注射K252 a，一种TrkB受体拮抗剂，显著降低了SB诱导的细胞增殖，阻断了SB诱导的巢蛋白表达和CREB激活，并减弱了SB的长期行为益处。总之，这些结果表明HDAC诱导的细胞增殖，迁移和分化需要BDNF-TrkB信号传导，并可能有助于SB在缺血性损伤后的长期有益作用。
In the healthy adult brain, neurogenesis normally occurs in the subventricular zone (SVZ) and hippocampal dentate gyrus (DG). Cerebral ischemia enhances neurogenesis in neurogenic and non-neurogenic regions of the ischemic brain of adult rodents. The present study demonstrated that post-insult treatment with an HDAC inhibitor, sodium butyrate (SB), stimulated the incorporation of bromo-2′-deoxyuridine (BrdU) in the SVZ, DG, striatum, and frontal cortex in the ischemic brain of rats subjected to permanent cerebral ischemia. SB treatment also increased the number of cells expressing polysialic acid-neural cell adhesion molecule (PSA-NCAM), nestin, GFAP, phospho-CREB, and brain-derived neurotrophic factor (BDNF) in various brain regions after cerebral ischemia. Furthermore, extensive co-localization of BrdU and PSA-NCAM was observed in multiple regions after ischemia, and SB treatment upregulated protein levels of BDNF, phospho-CREB and GFAP. Intraventricular injection of K252a, a TrkB receptor antagonist, markedly reduced SB-induced cell proliferation detected by BrdU and Ki67 in the ipsilateral SVZ, DG and other brain regions, blocked SB-induced nestin expression and CREB activation, and attenuated the long-lasting behavioral benefits of SB. Together, these results suggest that HDAC inhibitor-induced cell proliferation, migration and differentiation require BDNF-TrkB signaling and may contribute to SB’s long-term beneficial effects after ischemic injury.
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影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
影响因子：
5.3
作者：
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影响因子：
56.9
作者：
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DOI：
10.1124/jpet.107.120188
发表时间：
2007-06-01
影响因子：
3.5
作者：
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通讯作者：
Chuang, De-Maw
影响因子：
4.7
作者：
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通讯作者：
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