L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain.

L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain.
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DOI:
10.1155/2012/321406
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发表时间:
2012
期刊:
Parkinson's disease
影响因子:
--
通讯作者:
Wessinger WD
Wessinger WD
中科院分区:
其他
文献类型:
--
作者:
Inyushin MY;Huertas A;Kucheryavykh YV;Kucheryavykh LY;Tsydzik V;Sanabria P;Eaton MJ;Skatchkov SN;Rojas LV;Wessinger WD

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星形胶质细胞终足围绕脑血管,可以在帕金森病治疗药物的输送中发挥作用。然而,有没有以前的证据表明,在脑星形胶质细胞中的L-DOPA的LAT转运体的存在,除了在文化。使用系统的L-DOPA管理和膜片钳,组织化学和共聚焦显微镜的组合,我们发现,L-DOPA主要是积累在星形胶质细胞的细胞体,星形胶质细胞终足周围的血管,和周细胞。在大脑切片中:(1)星形胶质细胞暴露于ASP+,一种MPP+的荧光单胺类似物;(2)星形胶质细胞摄取的ASP+与L-DOPA荧光共定位于(3)神经胶质细胞体和附着于血管的尾足中;(4)这些星形胶质细胞具有由ASP+引起的生电转运体电流,但有趣的是不由L-DOPA引起,表明单胺和L-DOPA通过星形胶质细胞膜的不同途径。(5)周细胞和星形胶质细胞终足中单胺氧化酶(MAO B型)的分布模式与左旋多巴的积累模式相似。我们的结论是,星形胶质细胞控制左旋多巴的摄取和代谢,因此,可能发挥关键作用,在调节脑多巴胺水平在多巴胺相关疾病。这些数据还表明,不同的转运机制可能存在单胺和左旋多巴。
Astrocyte endfeet surround brain blood vessels and can play a role in the delivery of therapeutic drugs for Parkinson's disease. However, there is no previous evidence of the presence of LAT transporter for L-DOPA in brain astrocytes except in culture. Using systemic L-DOPA administration and a combination of patch clamp, histochemistry and confocal microscopy we found that L-DOPA is accumulated mainly in astrocyte cell bodies, astrocytic endfeet surrounding blood vessels, and pericytes. In brain slices: (1) astrocytes were exposed to ASP+, a fluorescent monoamine analog of MPP+; (2) ASP+ taken up by astrocytes was colocalized with L-DOPA fluorescence in (3) glial somata and in the endfeet attached to blood vessels; (4) these astrocytes have an electrogenic transporter current elicited by ASP+, but intriguingly not by L-DOPA, suggesting a different pathway for monoamines and L-DOPA via astrocytic membrane. (5) The pattern of monoamine oxidase (MAO type B) allocation in pericytes and astrocytic endfeet was similar to that of L-DOPA accumulation. We conclude that astrocytes control L-DOPA uptake and metabolism and, therefore, may play a key role in regulating brain dopamine level during dopamine-associated diseases. These data also suggest that different transporter mechanisms may exist for monoamines and L-DOPA.
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