Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's disease
The migration of peripheral bone-marrow-derived cells (BMDCs) to the brain was studied in a chronic mouse model of Parkinson's disease (PD). BMDCs expressing the enhanced green fluorescent protein (GFP) were aseptically obtained from C57 BL/6-EGFP-Tg mice and intravenously injected into C57 BL/...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-12-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996107001702 |
| _version_ | 1818610364334473216 |
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| author | Manuel Rodriguez Lydia Alvarez-Erviti Francisco J. Blesa Maria C. Rodríguez-Oroz Ainhoa Arina Ignacio Melero Luís Isaac Ramos Jose A. Obeso |
| author_facet | Manuel Rodriguez Lydia Alvarez-Erviti Francisco J. Blesa Maria C. Rodríguez-Oroz Ainhoa Arina Ignacio Melero Luís Isaac Ramos Jose A. Obeso |
| author_sort | Manuel Rodriguez |
| collection | DOAJ |
| description | The migration of peripheral bone-marrow-derived cells (BMDCs) to the brain was studied in a chronic mouse model of Parkinson's disease (PD). BMDCs expressing the enhanced green fluorescent protein (GFP) were aseptically obtained from C57 BL/6-EGFP-Tg mice and intravenously injected into C57 BL/6j mice which had received a total body irradiation of 8 Gy to induce bone marrow ablation. Implanted GFP-BMDCs replenished the bone marrow of irradiated mice, and progressively crossed the blood–brain barrier (BBB), penetrating different mesencephalic and telencephalic brain regions in the following months. The progressive degeneration of dopamine (DA) cells with a small daily dose (4 mg/kg/day for 20 days) of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) increased the penetration of GFP-BMDCs into the brain, particularly into those regions with marked DA innervation and which showed the clearest DA cell loss. BMDC penetration increased before the DA cell loss was evident and persisted for a long time after MPTP withdrawal. Under these conditions, most BMDCs differentiated into microglia (CD68 expression was observed in 50% of GFP cells 60 days after MPTP administration). BMDC-derived microglia showed morphological characteristics of cell activation, with the glial cell line-derived neurotrophic factor only being expressed in 3% of the cells. No differentiation into neurons (NeuN expression), astrocites (GFAP), cytotoxic lymphocytes (CD8) and T-helper lymphocytes (CD4) was observed. Taken together, the present data suggest that a significant portion of microglial cells is of a peripheral origin. Bearing in mind that microglial reaction is a significant part of the degenerative process in PD, the increase of BMDC penetration into DA-rich areas during DA cell degeneration and their differentiation into microglia suggest that cells coming across the BBB may participate in the neurodegeneration process. The precise role of such a cell inflow into the brain requires further study. Nevertheless, this may represent an opportunity to develop neuroprotective therapeutic strategies for PD. |
| first_indexed | 2024-12-16T15:13:15Z |
| format | Article |
| id | doaj.art-7825105996634e008555e1e3972bbfd6 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T15:13:15Z |
| publishDate | 2007-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-7825105996634e008555e1e3972bbfd62022-12-21T22:26:53ZengElsevierNeurobiology of Disease1095-953X2007-12-01283316325Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's diseaseManuel Rodriguez0Lydia Alvarez-Erviti1Francisco J. Blesa2Maria C. Rodríguez-Oroz3Ainhoa Arina4Ignacio Melero5Luís Isaac Ramos6Jose A. Obeso7Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain; Corresponding author. Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain. Fax: +34 922 319397.Department of Neurology and Neurosurgery, Clinica Universitaria, CIMA, University of Navarra, Pamplona, SpainDepartment of Neurology and Neurosurgery, Clinica Universitaria, CIMA, University of Navarra, Pamplona, SpainDepartment of Neurology and Neurosurgery, Clinica Universitaria, CIMA, University of Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), SpainGene Therapy and Department of Medicine, Clinica Universitaria, CIMA, University of Navarra, Pamplona, SpainGene Therapy and Department of Medicine, Clinica Universitaria, CIMA, University of Navarra, Pamplona, SpainOncology and Radiotherapy Department, CIMA, University of Navarra, Pamplona, SpainDepartment of Neurology and Neurosurgery, Clinica Universitaria, CIMA, University of Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), SpainThe migration of peripheral bone-marrow-derived cells (BMDCs) to the brain was studied in a chronic mouse model of Parkinson's disease (PD). BMDCs expressing the enhanced green fluorescent protein (GFP) were aseptically obtained from C57 BL/6-EGFP-Tg mice and intravenously injected into C57 BL/6j mice which had received a total body irradiation of 8 Gy to induce bone marrow ablation. Implanted GFP-BMDCs replenished the bone marrow of irradiated mice, and progressively crossed the blood–brain barrier (BBB), penetrating different mesencephalic and telencephalic brain regions in the following months. The progressive degeneration of dopamine (DA) cells with a small daily dose (4 mg/kg/day for 20 days) of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) increased the penetration of GFP-BMDCs into the brain, particularly into those regions with marked DA innervation and which showed the clearest DA cell loss. BMDC penetration increased before the DA cell loss was evident and persisted for a long time after MPTP withdrawal. Under these conditions, most BMDCs differentiated into microglia (CD68 expression was observed in 50% of GFP cells 60 days after MPTP administration). BMDC-derived microglia showed morphological characteristics of cell activation, with the glial cell line-derived neurotrophic factor only being expressed in 3% of the cells. No differentiation into neurons (NeuN expression), astrocites (GFAP), cytotoxic lymphocytes (CD8) and T-helper lymphocytes (CD4) was observed. Taken together, the present data suggest that a significant portion of microglial cells is of a peripheral origin. Bearing in mind that microglial reaction is a significant part of the degenerative process in PD, the increase of BMDC penetration into DA-rich areas during DA cell degeneration and their differentiation into microglia suggest that cells coming across the BBB may participate in the neurodegeneration process. The precise role of such a cell inflow into the brain requires further study. Nevertheless, this may represent an opportunity to develop neuroprotective therapeutic strategies for PD.http://www.sciencedirect.com/science/article/pii/S0969996107001702Bone marrowParkinson's diseaseMicrogliaBlood–brain barrier |
| spellingShingle | Manuel Rodriguez Lydia Alvarez-Erviti Francisco J. Blesa Maria C. Rodríguez-Oroz Ainhoa Arina Ignacio Melero Luís Isaac Ramos Jose A. Obeso Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's disease Neurobiology of Disease Bone marrow Parkinson's disease Microglia Blood–brain barrier |
| title | Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's disease |
| title_full | Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's disease |
| title_fullStr | Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's disease |
| title_full_unstemmed | Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's disease |
| title_short | Bone-marrow-derived cell differentiation into microglia: A study in a progressive mouse model of Parkinson's disease |
| title_sort | bone marrow derived cell differentiation into microglia a study in a progressive mouse model of parkinson s disease |
| topic | Bone marrow Parkinson's disease Microglia Blood–brain barrier |
| url | http://www.sciencedirect.com/science/article/pii/S0969996107001702 |
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