TY - JOUR
T1 - Intranigral Administration of β -Sitosterol- β -D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra
AU - Luna-Herrera, Claudia
AU - Martínez-Dávila, Irma A.
AU - Soto-Rojas, Luis O.
AU - Flores-Martinez, Yazmin M.
AU - Fernandez-Parrilla, Manuel A.
AU - Ayala-Davila, Jose
AU - León-Chavez, Bertha A.
AU - Soto-Rodriguez, Guadalupe
AU - Blanco-Alvarez, Victor M.
AU - Lopez-Salas, Francisco E.
AU - Gutierrez-Castillo, Maria E.
AU - Gatica-Garcia, Bismark
AU - Padilla-Viveros, America
AU - Bañuelos, Cecilia
AU - Reyes-Corona, David
AU - Espadas-Alvarez, Armando J.
AU - Garcés-Ramírez, Linda
AU - Hidalgo-Alegria, Oriana
AU - De La Cruz-López, Fidel
AU - Martinez-Fong, Daniel
N1 - Publisher Copyright:
© 2020 Claudia Luna-Herrera et al.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097231753&partnerID=8YFLogxK
U2 - 10.1155/2020/5907591
DO - 10.1155/2020/5907591
M3 - Artículo
C2 - 33282962
AN - SCOPUS:85097231753
SN - 2314-8861
VL - 2020
JO - Journal of Immunology Research
JF - Journal of Immunology Research
M1 - 5907591
ER -