Reduction of L-type amino acid transporter 1 mRNA expression in brain capillaries in a mouse model of Parkinson's disease

Sumio Ohtsuki, Hirofumi Yamaguchi, Young Sook Kang, Satoko Hori, Tetsuya Terasaki

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 7 d after MPTP treatment, mice showed a motor deficit and a loss of dopaminergic neurons. At the same time, Ltype 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.

Original languageEnglish
Pages (from-to)1250-1252
Number of pages3
JournalBiological and Pharmaceutical Bulletin
Volume33
Issue number7
DOIs
Publication statusPublished - 2010 Jul 16

Keywords

  • Blood-brain barrier
  • Brain capillary
  • L-type amino acid transporter 1
  • Parkinson's disease
  • Transporter

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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