Reduction of L-Type Amino Acid Transporter 1 mRNA Expression in Brain Capillaries in a Mouse Model of Parkinson's Disease
Reduction of L-Type Amino Acid Transporter 1 mRNA Expression in Brain Capillaries in a Mouse Model of Parkinson's Disease
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DOI：
10.1248/bpb.33.1250
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发表时间：
2010-07-01
影响因子：
2
通讯作者：
Terasaki, Tetsuya
中科院分区：
文献类型：
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作者：
Ohtsuki, Sumio;Yamaguchi, Hirofumi;Terasaki, Tetsuya
血脑屏障（BBB）表达的转运蛋白影响多巴胺能神经元的功能和帕金森病（PD）的药物治疗。本研究的目的是阐明1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）治疗的小鼠作为PD模型的BBB转运蛋白mRNA表达的变化，以了解BBB转运功能在PD中的病理生理作用。在MPTP治疗后7天，小鼠表现出运动缺陷和多巴胺能神经元的损失。与此同时，MPTP处理小鼠脑毛细血管组分中L型氨基酸转运体1（LAT 1）mRNA表达与生理盐水处理小鼠相比显著降低62.6%，而葡萄糖转运体1、肌酸转运体1、牛磺酸转运体、有机阳离子转运体2、5-羟色胺转运体、去甲肾上腺素转运体和多巴胺转运体。全脑LAT 1 mRNA表达在给药后1、3、5d无明显变化，但在给药后7 d下降46.3%。LAT 1介导包括酪氨酸在内的大型中性氨基酸以及PD治疗药物左旋多巴穿过BBB的转运。我们的研究结果表明，在帕金森病患者的血脑屏障LAT 1的表达减少可能会产生不利影响的氨基酸供应从循环血液和左旋多巴分布到大脑。
The blood brain barrier (BBB) expresses transporters that influence both dopaminergic neuronal function and drug therapy for Parkinson's disease (PD). The purpose of the present study was to clarify changes of transporter mRNA expression at the BBB in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a model of PD, in order to understand the pathophysiological role of BBB transport function in PD. At 7d after MPTP treatment, mice showed a motor deficit and a loss of dopaminergic neurons. At the same time, L-type amino acid transporter 1 (LAT1) mRNA expression in the brain capillary fraction of the MPTP-treated mice was significantly reduced by 62.6% compared with saline-treated mice, while no significant change was observed in the expression of glucose transporter 1, creatine transporter 1, taurine transporter, organic cation transporter 2, serotonin transporter, norepinephrine transporter and dopamine transporter. LAT1 mRNA expression in whole brain was not affected at 1, 3 and 5d after the treatment, but was reduced by 46.3% at 7d. LAT1 mediates the transport of large neutral amino acids, including tyrosine, as well as the PD-therapeutic drug levodopa, across the BBB. Our findings indicate that decreased LAT1 expression at the BBB in PD patients may adversely affect amino acid supply from the circulating blood and levodopa distribution into the brain.