Adaptive changes of extracellular amino acid concentrations in mouse dorsal striatum by 4-AP-induced cortical seizures
Adaptive changes of extracellular amino acid concentrations in mouse dorsal striatum by 4-AP-induced cortical seizures
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DOI：
10.1016/j.neuroscience.2015.03.043
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发表时间：
2015-06
期刊：
影响因子：
3.3
通讯作者：
T. Nagai;N. Takata;Y. Shinohara;H. Hirase
中科院分区：
文献类型：
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作者：
T. Nagai;N. Takata;Y. Shinohara;H. Hirase
纹状体是大脑皮层输出的主要目标。皮质纹状体投射已得到很好的描述，然而，长期皮质过度激活后纹状体中发生的神经化学变化仍有待研究。在这项研究中，使用微透析法测量了麻醉小鼠静息状态和 4-氨基吡啶 (4-AP) 诱导的皮质癫痫期间背侧纹状体的谷氨酸、GABA 和丙氨酸的细胞外水平。在诱导皮质癫痫发作的初级运动皮层局部应用 4-AP 后，纹状体 GABA 的细胞外水平在 60 分钟内增加了 40%。相比之下，纹状体谷氨酸的细胞外水平下降了 20%。此外，纹状体谷氨酸/天冬氨酸转运蛋白 (GLAST) 和谷氨酸转运蛋白 1 (GLT-1)（主要的星形胶质细胞高亲和力谷氨酸转运蛋白）的表面量往往会因 60 分钟内皮质癫痫发作而增加，这表明谷氨酸转运蛋白从内部储存中招募。 4-AP 还导致丙氨酸水平稳定增加，这被认为反映了神经元和星形胶质细胞中谷氨酸和丙酮酸的代谢。这些观察结果可能描绘了严重皮质癫痫发作引起的纹状体代谢的适应性变化。
The striatum is a major target of cerebral cortical output. The cortico-striatal projection has been well described, however, the neurochemical changes that occur in the striatum after prolonged cortical hyperactivation remain to be investigated. In this study, extracellular levels of glutamate, GABA, and alanine levels were measured in the dorsal striatum using microdialysis in anesthetized mice at resting condition and during 4-aminopyridine (4-AP)-induced cortical seizures. After topical application of 4-AP on the primary motor cortex that induced cortical seizures, the extracellular level of striatal GABA increased by 40% in 60 min. By contrast, the extracellular level of striatal glutamate decreased by 20%. Moreover, the surface amounts of striatal glutamate/aspartate transporter (GLAST) and glutamate transporter 1 (GLT-1), the major astrocytic high-affinity glutamate transporters, tended to increase by cortical seizures in 60 min, suggesting a recruitment of the glutamate transporters from internal stores. 4-AP also resulted in a steady increase of alanine levels which are thought to reflect glutamate and pyruvate metabolism in neurons and astrocytes. These observations possibly delineate adaptive changes of striatal metabolism by severe cortical seizures.