Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease
Charcot-Marie-Tooth type 1A (CMT1A) is a hereditary demyelinating neuropathy due to an increased genetic dosage of the peripheral myelin protein 22 (PMP22). The mechanisms leading from PMP22 overexpression to impairment of myelination are still unclear. We evaluated expression and processing of PMP2...
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| Format: | Article |
| Language: | English |
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Elsevier
2004-06-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996104000415 |
| _version_ | 1818615711611748352 |
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| author | Lucilla Nobbio Tiziana Vigo Michele Abbruzzese Giovanni Levi Claudio Brancolini Stefano Mantero Marina Grandis Luana Benedetti Gianluigi Mancardi Angelo Schenone |
| author_facet | Lucilla Nobbio Tiziana Vigo Michele Abbruzzese Giovanni Levi Claudio Brancolini Stefano Mantero Marina Grandis Luana Benedetti Gianluigi Mancardi Angelo Schenone |
| author_sort | Lucilla Nobbio |
| collection | DOAJ |
| description | Charcot-Marie-Tooth type 1A (CMT1A) is a hereditary demyelinating neuropathy due to an increased genetic dosage of the peripheral myelin protein 22 (PMP22). The mechanisms leading from PMP22 overexpression to impairment of myelination are still unclear. We evaluated expression and processing of PMP22, viability, proliferation, migration, motility and shaping properties, and ability of forming myelin of PMP22 transgenic (PMP22tg) Schwann cells in culture. In basal conditions, PMP22tg Schwann cells, although expressing higher PMP22 levels than control ones, show normal motility, migration and shaping properties. Addition of forskolin to the media induces an additional stimulation of PMP22 expression and results in an impairment of cells migration and motility, and a reduction of cell area and perimeter. Similarly, co-culturing transgenic Schwann cells with neurons causes an altered cells differentiation and an impairment of myelin formation. In conclusion, exposure of PMP22tg Schwann to the axon or to axonal-mimicking stimuli significantly affects the transition of transgenic Schwann cells to the myelinating phenotype. |
| first_indexed | 2024-12-16T16:38:15Z |
| format | Article |
| id | doaj.art-4fab7f8e7277422388a05f8643abd959 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T16:38:15Z |
| publishDate | 2004-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-4fab7f8e7277422388a05f8643abd9592022-12-21T22:24:24ZengElsevierNeurobiology of Disease1095-953X2004-06-01161263273Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A diseaseLucilla Nobbio0Tiziana Vigo1Michele Abbruzzese2Giovanni Levi3Claudio Brancolini4Stefano Mantero5Marina Grandis6Luana Benedetti7Gianluigi Mancardi8Angelo Schenone9Department of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyDepartment of Neurosciences, Ophthalmology and Genetics, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Centre National de la Recherche Scientifique UMR8572 CNRS-MNHN, 75005 Paris, France; Biology Section, Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy; Dulbecco Telethon Institute, CNR-ITB, 20090 Segrate Milan, ItalyCharcot-Marie-Tooth type 1A (CMT1A) is a hereditary demyelinating neuropathy due to an increased genetic dosage of the peripheral myelin protein 22 (PMP22). The mechanisms leading from PMP22 overexpression to impairment of myelination are still unclear. We evaluated expression and processing of PMP22, viability, proliferation, migration, motility and shaping properties, and ability of forming myelin of PMP22 transgenic (PMP22tg) Schwann cells in culture. In basal conditions, PMP22tg Schwann cells, although expressing higher PMP22 levels than control ones, show normal motility, migration and shaping properties. Addition of forskolin to the media induces an additional stimulation of PMP22 expression and results in an impairment of cells migration and motility, and a reduction of cell area and perimeter. Similarly, co-culturing transgenic Schwann cells with neurons causes an altered cells differentiation and an impairment of myelin formation. In conclusion, exposure of PMP22tg Schwann to the axon or to axonal-mimicking stimuli significantly affects the transition of transgenic Schwann cells to the myelinating phenotype.http://www.sciencedirect.com/science/article/pii/S0969996104000415CMT1AHereditary neuropathyPMP22Schwann cellAxonMotility |
| spellingShingle | Lucilla Nobbio Tiziana Vigo Michele Abbruzzese Giovanni Levi Claudio Brancolini Stefano Mantero Marina Grandis Luana Benedetti Gianluigi Mancardi Angelo Schenone Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease Neurobiology of Disease CMT1A Hereditary neuropathy PMP22 Schwann cell Axon Motility |
| title | Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease |
| title_full | Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease |
| title_fullStr | Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease |
| title_full_unstemmed | Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease |
| title_short | Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease |
| title_sort | impairment of pmp22 transgenic schwann cells differentiation in culture implications for charcot marie tooth type 1a disease |
| topic | CMT1A Hereditary neuropathy PMP22 Schwann cell Axon Motility |
| url | http://www.sciencedirect.com/science/article/pii/S0969996104000415 |
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