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

doi:10.1016/j.brainres.2006.04.078

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 journal › Article › peer-review

15 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 language	English
Pages (from-to)	1-11
Number of pages	11
Journal	Brain Research
Volume	1102
Issue number	1
DOIs	https://doi.org/10.1016/j.brainres.2006.04.078
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.brainres.2006.04.078

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title = "Control of dopamine-secretion by Tet-Off system in an in vivo model of parkinsonian rat",

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.",

keywords = "Cell therapy, Cerebrospinal fluid, Dopamine, Encapsulation, Parkinson's disease, Rat, Tet-Off system",

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

note = "Funding Information: We thank Drs. Masami Takahashi and Yoko Shoji-Kasai (Life Science Research Center, Mitsubishi Chemicals, Tokyo, Japan) for giving us PC12 cells (clone B3), Hideki Wakimoto for photographic work, Masako Arao and Tomoko Ujibashi for technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research and the Grant of the project for realization of regenerative medicine from the Ministry of Education, Culture, Sports, Science and Technology in Japan.",

year = "2006",

month = aug,

day = "2",

doi = "10.1016/j.brainres.2006.04.078",

language = "English",

volume = "1102",

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journal = "Molecular Brain Research",

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T1 - Control of dopamine-secretion by Tet-Off system in an in vivo model of parkinsonian rat

AU - Kobayashi, Kazuki

AU - Yasuhara, Takao

AU - Agari, Takashi

AU - Muraoka, Kenichiro

AU - Kameda, Masahiro

AU - Ji Yuan, wen

AU - Hayase, Hitoshi

AU - Matsui, Toshihiro

AU - Miyoshi, Yasuyuki

AU - Shingo, Tetsuro

AU - Date, Isao

N1 - Funding Information: We thank Drs. Masami Takahashi and Yoko Shoji-Kasai (Life Science Research Center, Mitsubishi Chemicals, Tokyo, Japan) for giving us PC12 cells (clone B3), Hideki Wakimoto for photographic work, Masako Arao and Tomoko Ujibashi for technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research and the Grant of the project for realization of regenerative medicine from the Ministry of Education, Culture, Sports, Science and Technology in Japan.

PY - 2006/8/2

Y1 - 2006/8/2

N2 - 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.

AB - 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.

KW - Cell therapy

KW - Cerebrospinal fluid

KW - Dopamine

KW - Encapsulation

KW - Parkinson's disease

KW - Rat

KW - Tet-Off system

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DO - 10.1016/j.brainres.2006.04.078

M3 - Article

C2 - 16806124

AN - SCOPUS:33746214604

SN - 0006-8993

VL - 1102

SP - 1

EP - 11

JO - Molecular Brain Research

JF - Molecular Brain Research

IS - 1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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