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 dopamine...
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2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/5907591 |
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| author | Claudia Luna-Herrera Irma A. Martínez-Dávila Luis O. Soto-Rojas Yazmin M. Flores-Martinez Manuel A. Fernandez-Parrilla Jose Ayala-Davila Bertha A. León-Chavez Guadalupe Soto-Rodriguez Victor M. Blanco-Alvarez Francisco E. Lopez-Salas Maria E. Gutierrez-Castillo Bismark Gatica-Garcia America Padilla-Viveros Cecilia Bañuelos David Reyes-Corona Armando J. Espadas-Alvarez Linda Garcés-Ramírez Oriana Hidalgo-Alegria Fidel De La Cruz-lópez Daniel Martinez-Fong |
| author_facet | Claudia Luna-Herrera Irma A. Martínez-Dávila Luis O. Soto-Rojas Yazmin M. Flores-Martinez Manuel A. Fernandez-Parrilla Jose Ayala-Davila Bertha A. León-Chavez Guadalupe Soto-Rodriguez Victor M. Blanco-Alvarez Francisco E. Lopez-Salas Maria E. Gutierrez-Castillo Bismark Gatica-Garcia America Padilla-Viveros Cecilia Bañuelos David Reyes-Corona Armando J. Espadas-Alvarez Linda Garcés-Ramírez Oriana Hidalgo-Alegria Fidel De La Cruz-lópez Daniel Martinez-Fong |
| author_sort | Claudia Luna-Herrera |
| collection | DOAJ |
| 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 | Article |
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| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
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| series | Journal of Immunology Research |
| spelling | doaj-art-0474752dbbf74b6ebd4ef45a062623d72025-02-03T06:43:30ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/59075915907591Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia NigraClaudia Luna-Herrera0Irma A. Martínez-Dávila1Luis O. Soto-Rojas2Yazmin M. Flores-Martinez3Manuel A. Fernandez-Parrilla4Jose Ayala-Davila5Bertha A. León-Chavez6Guadalupe Soto-Rodriguez7Victor M. Blanco-Alvarez8Francisco E. Lopez-Salas9Maria E. Gutierrez-Castillo10Bismark Gatica-Garcia11America Padilla-Viveros12Cecilia Bañuelos13David Reyes-Corona14Armando J. Espadas-Alvarez15Linda Garcés-Ramírez16Oriana Hidalgo-Alegria17Fidel De La Cruz-lópez18Daniel Martinez-Fong19Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu y Cda. Manuel Stampa s/n, C.P. 07738 Ciudad de México, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, San Pedro Zacatenco, MexicoFacultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios No. 1, Tlalnepantla, C.P. 54090 Edo. De México, MexicoPrograma Institucional de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Guillermo Massieu Helguera 239, C.P. 07320 Ciudad de México, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, San Pedro Zacatenco, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, San Pedro Zacatenco, MexicoFacultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Av.14 Sur y Av. San Claudio, Cd. Universitaria, Puebla, C.P. 72570 Puebla, MexicoFacultad de Medicina, Benemérita Universidad Autónoma de Puebla, 13 Sur 2702, Puebla, C.P. 72420 Puebla, MexicoFacultad de Medicina, Benemérita Universidad Autónoma de Puebla, 13 Sur 2702, Puebla, C.P. 72420 Puebla, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, San Pedro Zacatenco, MexicoDepartamento de Biociencias e Ingeniería, Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo, Instituto Politécnico Nacional, 30 de Junio de 1520 s/n, C.P. 07340 Ciudad de México, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, San Pedro Zacatenco, MexicoCoordinación General de Programas Multidisciplinarios, Programa Transdisciplinario en Desarrollo Científico y Tecnológico para la Sociedad, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, MexicoCoordinación General de Programas Multidisciplinarios, Programa Transdisciplinario en Desarrollo Científico y Tecnológico para la Sociedad, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, San Pedro Zacatenco, MexicoDepartamento de Biociencias e Ingeniería, Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo, Instituto Politécnico Nacional, 30 de Junio de 1520 s/n, C.P. 07340 Ciudad de México, MexicoDepartamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu y Cda. Manuel Stampa s/n, C.P. 07738 Ciudad de México, MexicoDepartamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu y Cda. Manuel Stampa s/n, C.P. 07738 Ciudad de México, MexicoDepartamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu y Cda. Manuel Stampa s/n, C.P. 07738 Ciudad de México, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508, C.P. 07360 Ciudad de México, San Pedro Zacatenco, MexicoChronic 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.http://dx.doi.org/10.1155/2020/5907591 |
| spellingShingle | Claudia Luna-Herrera Irma A. Martínez-Dávila Luis O. Soto-Rojas Yazmin M. Flores-Martinez Manuel A. Fernandez-Parrilla Jose Ayala-Davila Bertha A. León-Chavez Guadalupe Soto-Rodriguez Victor M. Blanco-Alvarez Francisco E. Lopez-Salas Maria E. Gutierrez-Castillo Bismark Gatica-Garcia America Padilla-Viveros Cecilia Bañuelos David Reyes-Corona Armando J. Espadas-Alvarez Linda Garcés-Ramírez Oriana Hidalgo-Alegria Fidel De La Cruz-lópez Daniel Martinez-Fong Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra Journal of Immunology Research |
| 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 |
| url | http://dx.doi.org/10.1155/2020/5907591 |
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