Abstract |
Neurotrophic factors exert considerable neuroprotective and neurorestorative effects in neurodegenerative diseases. Because neuronal progenitor cells have, at least in part, the potency to restore degenerated neuronal networks, transgenic high-dosage expression of neurotrophins by these cells in neurotransplantation may be advantageous. In the present study, a retroviral vector containing the gene of rat ciliary neurotrophic factor (rCNTF) was permanently transfected into a striatal neuronal progenitor cell line. Qualitative and quantitative analyses demonstrated a sustained expression of the transgene; i.e., rCNTF was present at the mRNA level and protein level. Moreover, cocultivation in separate chambers of transgenic CNTF-ST14A cells and CNTF-dependent TF1 cells exerted typical biological effects, such as increased proliferation and differentiation of the TF1 cells, indicating the functional integrity of the secreted recombinant neurotrophin. The CNTF-ST14A cells displayed improved stress response compared with native ST14A cells under differentiation conditions, i.e., at the nonpermissive temperature of 39 degrees C and after staurosporine exposure, respectively. This effect coincided with a relatively reduced apoptosis rate and a raised metabolic activity of CNTF-ST14A cells at 39 degrees C. Neurotransplantation of CNTF-ST14A cells in the rat quinolinic acid model of Huntington's disease showed a significant and sustained decline in pathological apomorphine-induced rotations compared with parental ST14A cells. We conclude that sustained functional transgene CNTF production improves stress response as well as metabolic activity, making CNTF-ST14A cells a promising tool for neurotransplantation in the quinolinic acid model of Huntington's disease.
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Authors | Sabine Weinelt, Sabine Peters, Peter Bauer, Eilhard Mix, Stefan J P Haas, Aline Dittmann, Stanislov Petrov, Andreas Wree, Elena Cattaneo, Rupert Knoblich, Ulf Strauss, Arndt Rolfs |
Journal | Journal of neuroscience research
(J Neurosci Res)
Vol. 71
Issue 2
Pg. 228-36
(Jan 15 2003)
ISSN: 0360-4012 [Print] United States |
PMID | 12503085
(Publication Type: Journal Article)
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Copyright | Copyright 2002 Wiley-Liss, Inc. |
Chemical References |
- 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium
- Ciliary Neurotrophic Factor
- Culture Media, Serum-Free
- Enzyme Inhibitors
- RNA, Messenger
- Tetrazolium Salts
- Tritium
- Quinolinic Acid
- Staurosporine
- Apomorphine
- Thymidine
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Topics |
- Animals
- Apomorphine
(toxicity)
- Apoptosis
(physiology)
- Blotting, Western
- Cell Differentiation
(physiology)
- Cell Division
(physiology)
- Cells, Cultured
- Ciliary Neurotrophic Factor
(metabolism, physiology)
- Coculture Techniques
- Corpus Striatum
(injuries)
- Culture Media, Serum-Free
(pharmacology)
- Disease Models, Animal
- Enzyme Inhibitors
(pharmacology)
- Fibroblasts
(metabolism)
- Gene Expression
- In Situ Nick-End Labeling
- Quinolinic Acid
(toxicity)
- RNA, Messenger
(biosynthesis)
- Rats
- Rats, Wistar
- Reverse Transcriptase Polymerase Chain Reaction
- Rotation
- Staurosporine
(pharmacology)
- Stem Cells
(physiology)
- Stress, Physiological
- Tetrazolium Salts
- Thermosensing
- Thymidine
(biosynthesis)
- Time Factors
- Transfection
- Tritium
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