Reduction of L-type amino acid transporter 1 mRNA expression in brain capillaries in a mouse model of Parkinson's disease.
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 7 d 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 5 d after the treatment, but was reduced by 46.3% at 7 d. 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.
Ohtsuki
Sumio
S
Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Yamaguchi
Hirofumi
H
Kang
Young-Sook
YS
Hori
Satoko
S
Terasaki
Tetsuya
T
D026905:Amino Acid Transport Systems / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000378:metabolism*; D017931:DNA Primers; D004195:Disease Models, Animal; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*
D026905:Amino Acid Transport Systems; D017931:DNA Primers; D012333:RNA, Messenger