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Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease

Parkinson’s disease is a neurodegenerative disorder characterized by the progressive death of dopaminergic (DA) neurons in the substantia nigra (SN), which leads to a loss of the neurotransmitter dopamine in the basal ganglia. Current treatments relieve the symptoms of the disease, but none stop or...

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Autores principales: Gonzalo-Gobernado, Rafael, Reimers, Diana, Casarejos, María José, Calatrava Ferreras, Lucía, Vallejo-Muñoz, Manuela, Jiménez-Escrig, Adriano, Diaz-Gil, Juan José, Ulzurrun de Asanza, Gonzalo M., Bazán, Eulalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287666/
https://www.ncbi.nlm.nih.gov/pubmed/32455921
http://dx.doi.org/10.3390/brainsci10050315
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author Gonzalo-Gobernado, Rafael
Reimers, Diana
Casarejos, María José
Calatrava Ferreras, Lucía
Vallejo-Muñoz, Manuela
Jiménez-Escrig, Adriano
Diaz-Gil, Juan José
Ulzurrun de Asanza, Gonzalo M.
Bazán, Eulalia
author_facet Gonzalo-Gobernado, Rafael
Reimers, Diana
Casarejos, María José
Calatrava Ferreras, Lucía
Vallejo-Muñoz, Manuela
Jiménez-Escrig, Adriano
Diaz-Gil, Juan José
Ulzurrun de Asanza, Gonzalo M.
Bazán, Eulalia
author_sort Gonzalo-Gobernado, Rafael
collection PubMed
description Parkinson’s disease is a neurodegenerative disorder characterized by the progressive death of dopaminergic (DA) neurons in the substantia nigra (SN), which leads to a loss of the neurotransmitter dopamine in the basal ganglia. Current treatments relieve the symptoms of the disease, but none stop or delay neuronal degeneration. Liver growth factor (LGF) is an albumin–bilirubin complex that stimulates axonal growth in the striatum and protects DA neurons in the SN of 6-hydroxydopamine-lesioned rats. Our previous results suggested that these effects observed in vivo are mediated by microglia and/or astrocytes. To determine if these cells are LGF targets, E14 (embryos from Sprague Dawley rats of 14 days) rat mesencephalic glial cultures were used. Treatment with 100 pg/mL of LGF up-regulated the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1/2 (ERK1/2) and the cyclic AMP response element binding protein (CREB) phosphorylation in glial cultures, and it increased the microglia marker Iba1 and tumor necrosis factor alpha (TNF-alpha) protein levels. The treatment of E14 midbrain neurons with a glial-conditioned medium from LGF-treated glial cultures (GCM-LGF) prevented the loss of DA neurons caused by 6-hydroxy-dopamine. This neuroprotective effect was not observed when GCM-LGF was applied in the presence of a blocking antibody of TNF-alpha activity. Altogether, our findings strongly suggest the involvement of microglia and TNF-alpha in the neuroprotective action of LGF on DA neurons observed in vitro.
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spelling pubmed-72876662020-06-15 Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease Gonzalo-Gobernado, Rafael Reimers, Diana Casarejos, María José Calatrava Ferreras, Lucía Vallejo-Muñoz, Manuela Jiménez-Escrig, Adriano Diaz-Gil, Juan José Ulzurrun de Asanza, Gonzalo M. Bazán, Eulalia Brain Sci Article Parkinson’s disease is a neurodegenerative disorder characterized by the progressive death of dopaminergic (DA) neurons in the substantia nigra (SN), which leads to a loss of the neurotransmitter dopamine in the basal ganglia. Current treatments relieve the symptoms of the disease, but none stop or delay neuronal degeneration. Liver growth factor (LGF) is an albumin–bilirubin complex that stimulates axonal growth in the striatum and protects DA neurons in the SN of 6-hydroxydopamine-lesioned rats. Our previous results suggested that these effects observed in vivo are mediated by microglia and/or astrocytes. To determine if these cells are LGF targets, E14 (embryos from Sprague Dawley rats of 14 days) rat mesencephalic glial cultures were used. Treatment with 100 pg/mL of LGF up-regulated the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1/2 (ERK1/2) and the cyclic AMP response element binding protein (CREB) phosphorylation in glial cultures, and it increased the microglia marker Iba1 and tumor necrosis factor alpha (TNF-alpha) protein levels. The treatment of E14 midbrain neurons with a glial-conditioned medium from LGF-treated glial cultures (GCM-LGF) prevented the loss of DA neurons caused by 6-hydroxy-dopamine. This neuroprotective effect was not observed when GCM-LGF was applied in the presence of a blocking antibody of TNF-alpha activity. Altogether, our findings strongly suggest the involvement of microglia and TNF-alpha in the neuroprotective action of LGF on DA neurons observed in vitro. MDPI 2020-05-22 /pmc/articles/PMC7287666/ /pubmed/32455921 http://dx.doi.org/10.3390/brainsci10050315 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gonzalo-Gobernado, Rafael
Reimers, Diana
Casarejos, María José
Calatrava Ferreras, Lucía
Vallejo-Muñoz, Manuela
Jiménez-Escrig, Adriano
Diaz-Gil, Juan José
Ulzurrun de Asanza, Gonzalo M.
Bazán, Eulalia
Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease
title Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease
title_full Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease
title_fullStr Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease
title_full_unstemmed Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease
title_short Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease
title_sort liver growth factor induces glia-associated neuroprotection in an in vitro model of parkinson´s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287666/
https://www.ncbi.nlm.nih.gov/pubmed/32455921
http://dx.doi.org/10.3390/brainsci10050315
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