Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra
The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1β (IL-1β) could be involved in mediating neuronal demise. However, it is unknown whether the...
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2006
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09699961_v24_n1_p183_Ferrari http://hdl.handle.net/20.500.12110/paper_09699961_v24_n1_p183_Ferrari |
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paper:paper_09699961_v24_n1_p183_Ferrari2023-06-08T15:59:09Z Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra Ferrari, Carina Cintia Pott Godoy, María Clara Tarelli, Rodolfo Chertoff, Mariela Sandra Juana Depino, Amaicha Mara Adenovector Akinesia Cytokine Inflammation Microglia Parkinson interleukin 1beta Adenovirus akinesia animal experiment animal model animal tissue article astrocyte cell activation cell death controlled study disease course dopaminergic nerve cell immunohistochemistry inflammatory infiltrate male microglia motor dysfunction nerve degeneration nonhuman pathogenesis pathophysiology priority journal protein expression rat scar formation substantia nigra virus recombinant Adenoviridae Animals Astrocytes Cell Death Cytokines Dopamine Genetic Vectors Glial Fibrillary Acidic Protein Interleukin-1 Macrophage Activation Macrophages Male Microglia Motor Activity Movement Disorders Nerve Degeneration Neuroglia Neurons Parkinson Disease, Secondary Rats Rats, Wistar Substantia Nigra The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1β (IL-1β) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1β in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1β in the adult rat SN using a recombinant adenovirus expressing IL-1β. The chronic expression of IL-1β for 60 days induced dopaminergic cell death in the SN and unilateral akinesia starting only at 21 days post-injection. Microglial cell activation and inflammatory cell infiltrate were associated with dopaminergic cell death and motor disabilities. Astrocytic activation was delayed and associated with scar formation. The chronic expression of a single proinflammatory cytokine as IL-1β in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1β per se is able to mediate inflammatory-mediated toxic effects in the SN if its expression is sustained. This model will be helpful to identify possible therapeutic targets related to inflammation-derived neurodegeneration in the SN. © 2006 Elsevier Inc. All rights reserved. Fil:Ferrari, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pott Godoy, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Tarelli, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Chertoff, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Depino, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09699961_v24_n1_p183_Ferrari http://hdl.handle.net/20.500.12110/paper_09699961_v24_n1_p183_Ferrari |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Adenovector Akinesia Cytokine Inflammation Microglia Parkinson interleukin 1beta Adenovirus akinesia animal experiment animal model animal tissue article astrocyte cell activation cell death controlled study disease course dopaminergic nerve cell immunohistochemistry inflammatory infiltrate male microglia motor dysfunction nerve degeneration nonhuman pathogenesis pathophysiology priority journal protein expression rat scar formation substantia nigra virus recombinant Adenoviridae Animals Astrocytes Cell Death Cytokines Dopamine Genetic Vectors Glial Fibrillary Acidic Protein Interleukin-1 Macrophage Activation Macrophages Male Microglia Motor Activity Movement Disorders Nerve Degeneration Neuroglia Neurons Parkinson Disease, Secondary Rats Rats, Wistar Substantia Nigra |
| spellingShingle |
Adenovector Akinesia Cytokine Inflammation Microglia Parkinson interleukin 1beta Adenovirus akinesia animal experiment animal model animal tissue article astrocyte cell activation cell death controlled study disease course dopaminergic nerve cell immunohistochemistry inflammatory infiltrate male microglia motor dysfunction nerve degeneration nonhuman pathogenesis pathophysiology priority journal protein expression rat scar formation substantia nigra virus recombinant Adenoviridae Animals Astrocytes Cell Death Cytokines Dopamine Genetic Vectors Glial Fibrillary Acidic Protein Interleukin-1 Macrophage Activation Macrophages Male Microglia Motor Activity Movement Disorders Nerve Degeneration Neuroglia Neurons Parkinson Disease, Secondary Rats Rats, Wistar Substantia Nigra Ferrari, Carina Cintia Pott Godoy, María Clara Tarelli, Rodolfo Chertoff, Mariela Sandra Juana Depino, Amaicha Mara Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra |
| topic_facet |
Adenovector Akinesia Cytokine Inflammation Microglia Parkinson interleukin 1beta Adenovirus akinesia animal experiment animal model animal tissue article astrocyte cell activation cell death controlled study disease course dopaminergic nerve cell immunohistochemistry inflammatory infiltrate male microglia motor dysfunction nerve degeneration nonhuman pathogenesis pathophysiology priority journal protein expression rat scar formation substantia nigra virus recombinant Adenoviridae Animals Astrocytes Cell Death Cytokines Dopamine Genetic Vectors Glial Fibrillary Acidic Protein Interleukin-1 Macrophage Activation Macrophages Male Microglia Motor Activity Movement Disorders Nerve Degeneration Neuroglia Neurons Parkinson Disease, Secondary Rats Rats, Wistar Substantia Nigra |
| description |
The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1β (IL-1β) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1β in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1β in the adult rat SN using a recombinant adenovirus expressing IL-1β. The chronic expression of IL-1β for 60 days induced dopaminergic cell death in the SN and unilateral akinesia starting only at 21 days post-injection. Microglial cell activation and inflammatory cell infiltrate were associated with dopaminergic cell death and motor disabilities. Astrocytic activation was delayed and associated with scar formation. The chronic expression of a single proinflammatory cytokine as IL-1β in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1β per se is able to mediate inflammatory-mediated toxic effects in the SN if its expression is sustained. This model will be helpful to identify possible therapeutic targets related to inflammation-derived neurodegeneration in the SN. © 2006 Elsevier Inc. All rights reserved. |
| author |
Ferrari, Carina Cintia Pott Godoy, María Clara Tarelli, Rodolfo Chertoff, Mariela Sandra Juana Depino, Amaicha Mara |
| author_facet |
Ferrari, Carina Cintia Pott Godoy, María Clara Tarelli, Rodolfo Chertoff, Mariela Sandra Juana Depino, Amaicha Mara |
| author_sort |
Ferrari, Carina Cintia |
| title |
Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra |
| title_short |
Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra |
| title_full |
Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra |
| title_fullStr |
Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra |
| title_full_unstemmed |
Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra |
| title_sort |
progressive neurodegeneration and motor disabilities induced by chronic expression of il-1β in the substantia nigra |
| publishDate |
2006 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09699961_v24_n1_p183_Ferrari http://hdl.handle.net/20.500.12110/paper_09699961_v24_n1_p183_Ferrari |
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| _version_ |
1768544741694111744 |