Control of dopamine-secretion by Tet-Off system in an in vivo model of parkinsonian rat

Kazuki Kobayashi, Takao Yasuhara, Takashi Agari, Kenichiro Muraoka, Masahiro Kameda, wen Ji Yuan, Hitoshi Hayase, Toshihiro Matsui, Yasuyuki Miyoshi, Tetsuro Shingo, Isao Date

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We established a PC12 cell line (PC12TH Tet-Off) in which human tyrosine hydroxylase (TH) expression can be negatively controlled by Doxycycline (Dox). First, dopamine (DA)-secretion from PC12TH Tet-Off cells was controlled by Dox-administration in a dose-responsive manner ranging from 0 to 100 ng/ml for 70 days in vitro. Furthermore, Parkinson's disease model of rats receiving encapsulated PC12TH Tet-Off cells displayed a significant decrease of dopamine concentration in the cerebrospinal fluid (CSF) and increase of the number of apomorphine-induced rotations by Dox-administration, as compared to transplanted rats without Dox-administration, although the significant decrease of the reduction ratio of DA concentration in the CSF with Dox-administration was recognized over time. At 2 months post-implantation, concentration of dopamine in the implanted striatum and from the retrieved capsules demonstrated that the control of DA-secretion could be partially achieved for 2 months in vivo. Our results support both the value of cell therapy using Tet-Off system and the technique of encapsulation might be a feasible option for Parkinson's disease especially in resolving the problem of dopamine oversupply in the future, although a more efficient way to control DA-secretion with quicker regulation and much titration of dose should be explored before clinical application.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBrain Research
Volume1102
Issue number1
DOIs
Publication statusPublished - Aug 2 2006

Keywords

  • Cell therapy
  • Cerebrospinal fluid
  • Dopamine
  • Encapsulation
  • Parkinson's disease
  • Rat
  • Tet-Off system

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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