Cargando…
Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra
Chronic consumption of β-sitosterol-β-D-glucoside (BSSG), a neurotoxin contained in cycad seeds, leads to Parkinson's disease in humans and rodents. Here, we explored whether a single intranigral administration of BSSG triggers neuroinflammation and neurotoxic A1 reactive astrocytes besides dop...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685831/ https://www.ncbi.nlm.nih.gov/pubmed/33282962 http://dx.doi.org/10.1155/2020/5907591 |
_version_ | 1783613246397218816 |
---|---|
author | Luna-Herrera, Claudia Martínez-Dávila, Irma A. Soto-Rojas, Luis O. Flores-Martinez, Yazmin M. Fernandez-Parrilla, Manuel A. Ayala-Davila, Jose León-Chavez, Bertha A. Soto-Rodriguez, Guadalupe Blanco-Alvarez, Victor M. Lopez-Salas, Francisco E. Gutierrez-Castillo, Maria E. Gatica-Garcia, Bismark Padilla-Viveros, America Bañuelos, Cecilia Reyes-Corona, David Espadas-Alvarez, Armando J. Garcés-Ramírez, Linda Hidalgo-Alegria, Oriana De La Cruz-lópez, Fidel Martinez-Fong, Daniel |
author_facet | Luna-Herrera, Claudia Martínez-Dávila, Irma A. Soto-Rojas, Luis O. Flores-Martinez, Yazmin M. Fernandez-Parrilla, Manuel A. Ayala-Davila, Jose León-Chavez, Bertha A. Soto-Rodriguez, Guadalupe Blanco-Alvarez, Victor M. Lopez-Salas, Francisco E. Gutierrez-Castillo, Maria E. Gatica-Garcia, Bismark Padilla-Viveros, America Bañuelos, Cecilia Reyes-Corona, David Espadas-Alvarez, Armando J. Garcés-Ramírez, Linda Hidalgo-Alegria, Oriana De La Cruz-lópez, Fidel Martinez-Fong, Daniel |
author_sort | Luna-Herrera, Claudia |
collection | PubMed |
description | Chronic consumption of β-sitosterol-β-D-glucoside (BSSG), a neurotoxin contained in cycad seeds, leads to Parkinson's disease in humans and rodents. Here, we explored whether a single intranigral administration of BSSG triggers neuroinflammation and neurotoxic A1 reactive astrocytes besides dopaminergic neurodegeneration. We injected 6 μg BSSG/1 μL DMSO or vehicle into the left substantia nigra and immunostained with antibodies against tyrosine hydroxylase (TH) together with markers of microglia (OX42), astrocytes (GFAP, S100β, C3), and leukocytes (CD45). We also measured nitric oxide (NO), lipid peroxidation (LPX), and proinflammatory cytokines (TNF-α, IL-1β, IL-6). The Evans blue assay was used to explore the blood-brain barrier (BBB) permeability. We found that BSSG activates NO production on days 15 and 30 and LPX on day 120. Throughout the study, high levels of TNF-α were present in BSSG-treated animals, whereas IL-1β was induced until day 60 and IL-6 until day 30. Immunoreactivity of activated microglia (899.0 ± 80.20%) and reactive astrocytes (651.50 ± 11.28%) progressively increased until day 30 and then decreased to remain 251.2 ± 48.8% (microglia) and 91.02 ± 39.8 (astrocytes) higher over controls on day 120. C3(+) cells were also GFAP and S100β immunoreactive, showing they were neurotoxic A1 reactive astrocytes. BBB remained permeable until day 15 when immune cell infiltration was maximum. TH immunoreactivity progressively declined, reaching 83.6 ± 1.8% reduction on day 120. Our data show that BSSG acute administration causes chronic neuroinflammation mediated by activated microglia, neurotoxic A1 reactive astrocytes, and infiltrated immune cells. The severe neuroinflammation might trigger Parkinson's disease in BSSG intoxication. |
format | Online Article Text |
id | pubmed-7685831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-76858312020-12-04 Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra Luna-Herrera, Claudia Martínez-Dávila, Irma A. Soto-Rojas, Luis O. Flores-Martinez, Yazmin M. Fernandez-Parrilla, Manuel A. Ayala-Davila, Jose León-Chavez, Bertha A. Soto-Rodriguez, Guadalupe Blanco-Alvarez, Victor M. Lopez-Salas, Francisco E. Gutierrez-Castillo, Maria E. Gatica-Garcia, Bismark Padilla-Viveros, America Bañuelos, Cecilia Reyes-Corona, David Espadas-Alvarez, Armando J. Garcés-Ramírez, Linda Hidalgo-Alegria, Oriana De La Cruz-lópez, Fidel Martinez-Fong, Daniel J Immunol Res Research Article Chronic consumption of β-sitosterol-β-D-glucoside (BSSG), a neurotoxin contained in cycad seeds, leads to Parkinson's disease in humans and rodents. Here, we explored whether a single intranigral administration of BSSG triggers neuroinflammation and neurotoxic A1 reactive astrocytes besides dopaminergic neurodegeneration. We injected 6 μg BSSG/1 μL DMSO or vehicle into the left substantia nigra and immunostained with antibodies against tyrosine hydroxylase (TH) together with markers of microglia (OX42), astrocytes (GFAP, S100β, C3), and leukocytes (CD45). We also measured nitric oxide (NO), lipid peroxidation (LPX), and proinflammatory cytokines (TNF-α, IL-1β, IL-6). The Evans blue assay was used to explore the blood-brain barrier (BBB) permeability. We found that BSSG activates NO production on days 15 and 30 and LPX on day 120. Throughout the study, high levels of TNF-α were present in BSSG-treated animals, whereas IL-1β was induced until day 60 and IL-6 until day 30. Immunoreactivity of activated microglia (899.0 ± 80.20%) and reactive astrocytes (651.50 ± 11.28%) progressively increased until day 30 and then decreased to remain 251.2 ± 48.8% (microglia) and 91.02 ± 39.8 (astrocytes) higher over controls on day 120. C3(+) cells were also GFAP and S100β immunoreactive, showing they were neurotoxic A1 reactive astrocytes. BBB remained permeable until day 15 when immune cell infiltration was maximum. TH immunoreactivity progressively declined, reaching 83.6 ± 1.8% reduction on day 120. Our data show that BSSG acute administration causes chronic neuroinflammation mediated by activated microglia, neurotoxic A1 reactive astrocytes, and infiltrated immune cells. The severe neuroinflammation might trigger Parkinson's disease in BSSG intoxication. Hindawi 2020-11-16 /pmc/articles/PMC7685831/ /pubmed/33282962 http://dx.doi.org/10.1155/2020/5907591 Text en Copyright © 2020 Claudia Luna-Herrera et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Luna-Herrera, Claudia Martínez-Dávila, Irma A. Soto-Rojas, Luis O. Flores-Martinez, Yazmin M. Fernandez-Parrilla, Manuel A. Ayala-Davila, Jose León-Chavez, Bertha A. Soto-Rodriguez, Guadalupe Blanco-Alvarez, Victor M. Lopez-Salas, Francisco E. Gutierrez-Castillo, Maria E. Gatica-Garcia, Bismark Padilla-Viveros, America Bañuelos, Cecilia Reyes-Corona, David Espadas-Alvarez, Armando J. Garcés-Ramírez, Linda Hidalgo-Alegria, Oriana De La Cruz-lópez, Fidel Martinez-Fong, Daniel Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra |
title | Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra |
title_full | Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra |
title_fullStr | Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra |
title_full_unstemmed | Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra |
title_short | Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra |
title_sort | intranigral administration of β-sitosterol-β-d-glucoside elicits neurotoxic a1 astrocyte reactivity and chronic neuroinflammation in the rat substantia nigra |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685831/ https://www.ncbi.nlm.nih.gov/pubmed/33282962 http://dx.doi.org/10.1155/2020/5907591 |
work_keys_str_mv | AT lunaherreraclaudia intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT martinezdavilairmaa intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT sotorojasluiso intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT floresmartinezyazminm intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT fernandezparrillamanuela intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT ayaladavilajose intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT leonchavezberthaa intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT sotorodriguezguadalupe intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT blancoalvarezvictorm intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT lopezsalasfranciscoe intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT gutierrezcastillomariae intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT gaticagarciabismark intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT padillaviverosamerica intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT banueloscecilia intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT reyescoronadavid intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT espadasalvarezarmandoj intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT garcesramirezlinda intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT hidalgoalegriaoriana intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT delacruzlopezfidel intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra AT martinezfongdaniel intranigraladministrationofbsitosterolbdglucosideelicitsneurotoxica1astrocytereactivityandchronicneuroinflammationintheratsubstantianigra |