Genetic control of astrocyte function in neural circuits.
Genetic control of astrocyte function in neural circuits.
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DOI：
10.3389/fncel.2015.00310
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发表时间：
2015
影响因子：
5.3
通讯作者：
Kirchhoff F
中科院分区：
文献类型：
--
作者：
Jahn HM;Scheller A;Kirchhoff F
在过去的二十年中，已经开发了许多影响体内细胞功能的遗传方法。目前最先进的技术允许在给定组织实质的复杂组织内的不同细胞群中选择性地切换基因功能。他莫昔芬诱导的 Cre/loxP 基因重组和多西环素依赖性基因表达调节可能是最流行的遗传范例。在这里，我们将回顾这两种策略的应用，同时重点关注中枢神经系统（CNS）中星形胶质细胞和神经元的相互作用及其对整个生物体的影响。通过选择性删除神经胶质递质受体来消除神经胶质对神经元活动的感知，证明了星形胶质细胞对学习和记忆等高级认知功能或肌肉协调的更基本的身体控制的影响。有趣的是，干扰神经胶质的输出，即神经胶质递质的释放可以极大地改变动物的生理机能，例如睡眠行为。此外，此类遗传方法也已用于恢复星形胶质细胞功能。在这些研究中，采用了两种替代方法来实现星形胶质细胞的正确遗传靶向：使用人胶质纤维酸性蛋白（GFAP）启动子的转基因或同源重组到谷氨酸-天冬氨酸转运蛋白（GLAST）基因座。我们将重点介绍与其用途相关的特定属性。
During the last two decades numerous genetic approaches affecting cell function in vivo have been developed. Current state-of-the-art technology permits the selective switching of gene function in distinct cell populations within the complex organization of a given tissue parenchyma. The tamoxifen-inducible Cre/loxP gene recombination and the doxycycline-dependent modulation of gene expression are probably the most popular genetic paradigms. Here, we will review applications of these two strategies while focusing on the interactions of astrocytes and neurons in the central nervous system (CNS) and their impact for the whole organism. Abolishing glial sensing of neuronal activity by selective deletion of glial transmitter receptors demonstrated the impact of astrocytes for higher cognitive functions such as learning and memory, or the more basic body control of muscle coordination. Interestingly, also interfering with glial output, i.e., the release of gliotransmitters can drastically change animal’s physiology like sleeping behavior. Furthermore, such genetic approaches have also been used to restore astrocyte function. In these studies two alternatives were employed to achieve proper genetic targeting of astrocytes: transgenes using the promoter of the human glial fibrillary acidic protein (GFAP) or homologous recombination into the glutamate-aspartate transporter (GLAST) locus. We will highlight their specific properties that could be relevant for their use.