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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/10/5/315 |
| _version_ | 1797567277877428224 |
|---|---|
| author | Rafael Gonzalo-Gobernado Diana Reimers María José Casarejos Lucía Calatrava Ferreras Manuela Vallejo-Muñoz Adriano Jiménez-Escrig Juan José Diaz-Gil Gonzalo M. Ulzurrun de Asanza Eulalia Bazán |
| author_facet | Rafael Gonzalo-Gobernado Diana Reimers María José Casarejos Lucía Calatrava Ferreras Manuela Vallejo-Muñoz Adriano Jiménez-Escrig Juan José Diaz-Gil Gonzalo M. Ulzurrun de Asanza Eulalia Bazán |
| author_sort | Rafael Gonzalo-Gobernado |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T19:39:23Z |
| format | Article |
| id | doaj.art-214feac5412942e1bca58ac6f8341785 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T19:39:23Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-214feac5412942e1bca58ac6f83417852023-11-20T01:22:24ZengMDPI AGBrain Sciences2076-34252020-05-0110531510.3390/brainsci10050315Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s DiseaseRafael Gonzalo-Gobernado0Diana Reimers1María José Casarejos2Lucía Calatrava Ferreras3Manuela Vallejo-Muñoz4Adriano Jiménez-Escrig5Juan José Diaz-Gil6Gonzalo M. Ulzurrun de Asanza7Eulalia Bazán8Servicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurología, Hospital Ramón y Cajal, 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainParkinson’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.https://www.mdpi.com/2076-3425/10/5/315liver growth factorLGFParkinson´s diseaseglial culturesneuroprotection6-hydroxy-dopamine |
| spellingShingle | Rafael Gonzalo-Gobernado Diana Reimers María José Casarejos Lucía Calatrava Ferreras Manuela Vallejo-Muñoz Adriano Jiménez-Escrig Juan José Diaz-Gil Gonzalo M. Ulzurrun de Asanza Eulalia Bazán Liver Growth Factor Induces Glia-Associated Neuroprotection in an In Vitro Model of Parkinson´s Disease Brain Sciences liver growth factor LGF Parkinson´s disease glial cultures neuroprotection 6-hydroxy-dopamine |
| 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 | liver growth factor LGF Parkinson´s disease glial cultures neuroprotection 6-hydroxy-dopamine |
| url | https://www.mdpi.com/2076-3425/10/5/315 |
| work_keys_str_mv | AT rafaelgonzalogobernado livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT dianareimers livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT mariajosecasarejos livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT luciacalatravaferreras livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT manuelavallejomunoz livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT adrianojimenezescrig livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT juanjosediazgil livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT gonzalomulzurrundeasanza livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease AT eulaliabazan livergrowthfactorinducesgliaassociatedneuroprotectioninaninvitromodelofparkinsonsdisease |