Deep brain stimulation results in local glutamate and adenosine release: investigation into the role of astrocytes.
Deep brain stimulation results in local glutamate and adenosine release: investigation into the role of astrocytes.
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DOI：
10.1227/01.neu.0000371988.73620.4c
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发表时间：
2010-08
期刊：
影响因子：
4.8
通讯作者：
Lee KH
中科院分区：
文献类型：
--
作者：
Tawfik VL;Chang SY;Hitti FL;Roberts DW;Leiter JC;Jovanovic S;Lee KH
一些神经系统疾病可以通过脑深部刺激来治疗；然而，其消除与帕金森病和癫痫等多种疾病相关的振荡现象的能力的机制仍然很大程度上未知。在这项研究中，我们试图研究特定神经递质在深部脑刺激（DBS）中的作用，并确定非神经元细胞在其作用机制中的作用。我们在体外使用雪貂丘脑切片制剂，其表现出自发的纺锤体振荡，以确定高频刺激对神经递质释放的影响。然后，我们使用体外星形胶质细胞培养物进行了实验，以研究神经胶质递质释放在 HFS 介导的纺锤体振荡消除中的作用。在这一系列的实验中，我们证明雪貂切片中谷氨酸和腺苷的释放能够消除自发的纺锤体振荡。在 Na+ 通道阻滞剂河豚毒素 (TTX) 存在的情况下，仍会引起谷氨酸释放，但会被囊泡 H+-ATP 酶抑制剂巴弗洛霉素和钙螯合剂 BAPTA-AM 消除。此外，纯化的原代星形胶质细胞培养物的电刺激能够引起细胞内钙瞬变和谷氨酸释放，并且在这种情况下BAPTA-AM的浴应用抑制谷氨酸释放。这些结果表明，囊泡星形细胞神经递质释放可能是 DBS 能够实现临床获益的重要机制。
Several neurologic disorders are treated with deep brain stimulation; however, the mechanism underlying its ability to abolish oscillatory phenomena associated with diseases as diverse as Parkinson's and epilepsy remain largely unknown. In this study we sought to investigate the role of specific neurotransmitters in deep brain stimulation (DBS) and determine the role of non-neuronal cells in its mechanism of action. We used the ferret thalamic slice preparation in vitro, which exhibits spontaneous spindle oscillations, in order to determine the effect of high-frequency stimulation on neurotransmitter release. We then performed experiments using an in vitro astrocyte culture to investigate the role of glial transmitter release in HFS-mediated abolishment of spindle oscillations. In this series of experiments we demonstrated that glutamate and adenosine release in ferret slices was able to abolish spontaneous spindle oscillations. The glutamate release was still evoked in the presence of the Na+ channel blocker tetrodotoxin (TTX), but was eliminated with the vesicular H+-ATPase inhibitor, bafilomycin, and the calcium chelator, BAPTA-AM. Furthermore, electrical stimulation of purified primary astrocytic cultures was able to evoke intracellular calcium transients and glutamate release, and bath application of BAPTA-AM inhibited glutamate release in this setting. These results suggest that vesicular astrocytic neurotransmitter release may be an important mechanism by which DBS is able to achieve clinical benefits.