Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium-dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury.
Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium-dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury.
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DOI：
10.1111/j.1460-9568.2011.07888.x
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Kernie SG
中科院分区：
文献类型：
--
作者：
Gilley JA;Kernie SG
利用一只用绿色荧光蛋白标记巢蛋白表达前体的转基因小鼠(Mus Musculus)，我们先前研究了GLTI和Glast在体内早期神经前体细胞上的表达。为了解决它们在这个细胞群体中的功能作用，我们操纵了它们在从齿状回分离的P7神经球中的表达。我们观察到，GLTI或Glast基因敲除与BrdU掺入减少和神经球形成有关。此外，我们确定这两种谷氨酸转运体都以钙和代谢性谷氨酸受体依赖的方式调节祖细胞的增殖。为了解决这在体内的相关性，我们使用获得性脑损伤的模型，这是已知的诱导海马神经发生的模型。我们观察到，GLTI和Glast在脑损伤后的祖细胞中特异性上调，并且这种上调的表达持续了数周。此外，我们发现，在祖代群体中谷氨酸转运体表达增加的反复损伤的动物对随后的损伤诱导的增殖具有抵抗力。这些结果表明，GLTI和Glast在体外对钙依赖的增殖具有负性调节作用，它们在损伤后的上调与脑创伤后的增殖减少有关。
Using a transgenic mouse (mus musculus) that labels nestin-expressing progenitors with eGFP, we previously characterized the expression of GltI and Glast on early neural progenitors in vivo. To address their functional role in this cell population, we manipulated their expression in P7 neurospheres isolated from the dentate gyrus. We observed that knockdown of GltI or Glast was associated with decreased BrdU incorporation and neurosphere formation. Moreover, we determined that both glutamate transporters regulate progenitor proliferation in a calcium- and metabotropic glutamate receptor-dependent manner. To address the relevance of this in vivo, we utilized models of acquired brain injury, which are known to induce hippocampal neurogenesis. We observed that GltI and Glast are specifically upregulated in progenitors following brain injury and that this increased expression is maintained for many weeks. Additionally, we found that recurrently injured animals with increased expression of glutamate transporters within the progenitor population were resistant to subsequent injury-induced proliferation. These findings demonstrate that GltI and Glast negatively regulate calcium-dependent proliferation in vitro and their upregulation after injury is associated with decreased proliferation after brain trauma.
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影响因子：
4.2
作者：
Kernie, SG;Erwin, TM;Parada, LF
通讯作者：
Parada, LF
影响因子：
6.3
作者：
Koch, Joshua D.;Miles, Darryl K.;Kernie, Steven G.
通讯作者：
Kernie, Steven G.
影响因子：
4.1
作者：
Bullock, R;Zauner, A;Young, HF
通讯作者：
Young, HF
DOI：
10.1002/0470870834.ch14
发表时间：
2000-01-01
期刊：
NEURAL TRANSPLANTATION IN NEURODEGENERATIVE DISEASE: CURRENT STATUS AND NEW DIRECTIONS
影响因子：
--
作者：
Kempermann, G;Gage, FH
通讯作者：
Gage, FH
DOI：
10.1523/jneurosci.5265-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Blaiss CA;Yu TS;Zhang G;Chen J;Dimchev G;Parada LF;Powell CM;Kernie SG
通讯作者：
Kernie SG