FACS identifies unique cocaine-induced gene regulation in selectively activated adult striatal neurons.

FACS identifies unique cocaine-induced gene regulation in selectively activated adult striatal neurons.
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FACS鉴定出选择性活化的成年纹状体神经元中独特的可卡因诱导的基因调节。

DOI:
10.1523/jneurosci.6195-10.2011
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发表时间:
2011-03-16
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
通讯作者:
Hope BT
Hope BT
中科院分区:
其他
文献类型:
--
作者:
Guez-Barber D;Fanous S;Golden SA;Schrama R;Koya E;Stern AL;Bossert JM;Harvey BK;Picciotto MR;Hope BT

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对神经活动标记 Fos 的大量研究表明,可卡因仅激活一小部分稀疏分布的纹状体神经元。到目前为止,还没有有效的方法来评估这些激活的神经元内特异性诱导的神经适应。我们使用荧光激活细胞分选 (FACS) 来纯化幼稚和可卡因致敏的 cfos-lacZ 转基因大鼠在可卡因诱导的运动过程中激活的纹状体神经元。激活的神经元用针对 β-半乳糖苷酶(lacZ 基因的蛋白质产物)的抗体进行标记。可卡因选择性地在一小部分激活的神经元中诱导独特的基因表达谱,而在大多数非激活的神经元中没有观察到这种情况。这些基因包括早期基因 arc、fosB 和 nr4a3 水平的改变,以及参与 p38 MAPK 信号传导和细胞类型特异性的基因。我们建议这种 FACS 方法可用于研究编码滥用药物和其他习得行为的行为影响的特定神经元的分子神经适应。
Numerous studies with the neural activity marker Fos indicate that cocaine activates only a small proportion of sparsely distributed striatal neurons. Until now, efficient methods were not available to assess neuroadaptations induced specifically within these activated neurons. We used fluorescence-activated cell sorting (FACS) to purify striatal neurons activated during cocaine-induced locomotion in naïve and cocaine-sensitized cfos-lacZ transgenic rats. Activated neurons were labeled with an antibody against β-galactosidase, the protein product of the lacZ gene. Cocaine induced a unique gene expression profile selectively in the small proportion of activated neurons that was not observed in the non-activated majority of neurons. These genes included altered levels of the immediate early genes arc, fosB, and nr4a3, as well as genes involved in p38 MAPK signaling and cell-type specificity. We propose that this FACS method can be used to study molecular neuroadaptations in specific neurons encoding the behavioral effects of abused drugs and other learned behaviors.