Laser-scanning astrocyte mapping reveals increased glutamate-responsive domain size and disrupted maturation of glutamate uptake following neonatal cortical freeze-lesion.
Laser-scanning astrocyte mapping reveals increased glutamate-responsive domain size and disrupted maturation of glutamate uptake following neonatal cortical freeze-lesion.
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DOI：
10.3389/fncel.2014.00277
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发表时间：
2014
影响因子：
5.3
通讯作者：
Dulla CG
中科院分区：
文献类型：
--
作者：
Armbruster M;Hampton D;Yang Y;Dulla CG
星形胶质细胞摄取谷氨酸形成细胞外神经递质动力学、受体激活和突触发生。在发育过程中，谷氨酸转运变得更加强劲。新生儿脑损伤如何影响谷氨酸转运的功能成熟仍然没有答案。新生儿脑损伤可导致发育迟缓、认知丧失和癫痫;已知谷氨酸转运的中断可引起突触发生、受体激活和癫痫发作的变化。使用新生儿冷冻损伤（FL）模型，我们研究了如何侮辱影响星形胶质细胞谷氨酸转运的成熟。由于损伤发生在出生当天，此时星形胶质细胞在功能上仍然不成熟，因此该模型是鉴定损伤后星形胶质细胞成熟变化的理想模型。已知在该模型中发生反应性星形胶质细胞增多、星形胶质细胞增殖和体外过度兴奋。为了更好地探测星形胶质细胞谷氨酸转运的空间精度，我们开发了一种新的技术，激光扫描星形胶质细胞映射（LSAM），它结合了谷氨酸转运电流（TC）记录从星形胶质细胞与激光扫描谷氨酸光解。LSAM使我们能够确定单个星形胶质细胞可以转运谷氨酸的区域，并量化该区域内谷氨酸清除动力学速率的空间异质性。使用LSAM，我们报告说，皮质星形胶质细胞有一个增加的谷氨酸反应区后FL和TC有更快的衰减时间在远端，相比近端的过程。此外，从GLAST-到GLT-1主导的清除发育转变被打乱以下FL。这些研究结果介绍了一种新的方法来探测星形胶质细胞谷氨酸的摄取，并表明，新生儿皮质FL破坏皮质星形胶质细胞的功能成熟。
Astrocytic uptake of glutamate shapes extracellular neurotransmitter dynamics, receptor activation, and synaptogenesis. During development, glutamate transport becomes more robust. How neonatal brain insult affects the functional maturation of glutamate transport remains unanswered. Neonatal brain insult can lead to developmental delays, cognitive losses, and epilepsy; the disruption of glutamate transport is known to cause changes in synaptogenesis, receptor activation, and seizure. Using the neonatal freeze-lesion (FL) model, we have investigated how insult affects the maturation of astrocytic glutamate transport. As lesioning occurs on the day of birth, a time when astrocytes are still functionally immature, this model is ideal for identifying changes in astrocyte maturation following insult. Reactive astrocytosis, astrocyte proliferation, and in vitro hyperexcitability are known to occur in this model. To probe astrocyte glutamate transport with better spatial precision we have developed a novel technique, Laser Scanning Astrocyte Mapping (LSAM), which combines glutamate transport current (TC) recording from astrocytes with laser scanning glutamate photolysis. LSAM allows us to identify the area from which a single astrocyte can transport glutamate and to quantify spatial heterogeneity in the rate of glutamate clearance kinetics within that domain. Using LSAM, we report that cortical astrocytes have an increased glutamate-responsive area following FL and that TCs have faster decay times in distal, as compared to proximal processes. Furthermore, the developmental shift from GLAST- to GLT-1-dominated clearance is disrupted following FL. These findings introduce a novel method to probe astrocyte glutamate uptake and show that neonatal cortical FL disrupts the functional maturation of cortical astrocytes.
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影响因子：
6.1
作者：
Andresen, Lauren;Hampton, David;Taylor-Weiner, Amaro;Morel, Lydie;Yang, Yongjie;Maguire, Jamie;Dulla, Chris G.
通讯作者：
Dulla, Chris G.
影响因子：
1.9
作者：
Crino, PB
通讯作者：
Crino, PB
影响因子：
6.1
作者：
Dulla, C. G.;Tani, H.;Huguenard, J. R.
通讯作者：
Huguenard, J. R.
影响因子：
2.5
作者：
Jacobs, KM;Prince, DA
通讯作者：
Prince, DA
影响因子：
5.3
作者：
Diamond, JS
通讯作者：
Diamond, JS