Control of dopamine-secretion by Tet-Off system in an in vivo model of parkinsonian rat
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2006 |
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| Erschienen: |
2006 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1102 |
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| Enthalten in: |
Brain research - 1102(2006), 1 vom: 02. Aug., Seite 1-11 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kobayashi, Kazuki [VerfasserIn] |
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| Anmerkungen: |
Date Completed 19.09.2006 Date Revised 21.11.2013 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM163805369 |
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| 041 | |a eng | ||
| 100 | 1 | |a Kobayashi, Kazuki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Control of dopamine-secretion by Tet-Off system in an in vivo model of parkinsonian rat |
| 264 | 1 | |c 2006 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 19.09.2006 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiporters |2 NLM | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a Dopamine Agonists |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a tetA protein, Bacteria |2 NLM | |
| 650 | 7 | |a Oxidopamine |2 NLM | |
| 650 | 7 | |a 8HW4YBZ748 |2 NLM | |
| 650 | 7 | |a Tyrosine 3-Monooxygenase |2 NLM | |
| 650 | 7 | |a EC 1.14.16.2 |2 NLM | |
| 650 | 7 | |a Doxycycline |2 NLM | |
| 650 | 7 | |a N12000U13O |2 NLM | |
| 650 | 7 | |a Apomorphine |2 NLM | |
| 650 | 7 | |a N21FAR7B4S |2 NLM | |
| 650 | 7 | |a Dopamine |2 NLM | |
| 650 | 7 | |a VTD58H1Z2X |2 NLM | |
| 700 | 1 | |a Yasuhara, Takao |e verfasserin |4 aut | |
| 700 | 1 | |a Agari, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Muraoka, Kenichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Kameda, Masahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Ji Yuan, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Hayase, Hitoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Matsui, Toshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Miyoshi, Yasuyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Shingo, Tetsuro |e verfasserin |4 aut | |
| 700 | 1 | |a Date, Isao |e verfasserin |4 aut | |
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