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Reduction of L-Type Amino Acid Transporter 1 mRNA Expression in Brain Capillaries in a Mouse Model of Parkinson's Disease

Authors
Ohtsuki, SumioYamaguchi, HirofumiKang, Young-SookHori, SatokoTerasaki, Tetsuya
Issue Date
Jul-2010
Publisher
PHARMACEUTICAL SOC JAPAN
Keywords
blood brain barrier; L-type amino acid transporter 1; Parkinson' s disease; brain capillary; transporter
Citation
BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.33, no.7, pp.1250 - 1252
Journal Title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume
33
Number
7
Start Page
1250
End Page
1252
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13178
DOI
10.1248/bpb.33.1250
ISSN
0918-6158
Abstract
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.
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