Distinctive Toll-like Receptors Gene Expression and Glial Response in Different Brain Regions of Natural Scrapie

García-Martínez, Mirta (Universidad de Zaragoza) ; Cortez, Leonardo M. ; Otero, Alicia (Universidad de Zaragoza) ; Betancor, Marina (Universidad de Zaragoza) ; Serrano-Pérez, Beatriz ; Bolea, Rosa (Universidad de Zaragoza) ; Badiola, Juan J. (Universidad de Zaragoza) ; Garza, María Carmen (Universidad de Zaragoza)

Resumen: Prion diseases are chronic and fatal neurodegenerative diseases characterized by the accumulation of disease-specific prion protein (PrPSc), spongiform changes, neuronal loss, and gliosis. Growing evidence shows that the neuroinflammatory response is a key component of prion diseases and contributes to neurodegeneration. Toll-like receptors (TLRs) have been proposed as important mediators of innate immune responses triggered in the central nervous system in other human neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. However, little is known about the role of TLRs in prion diseases, and their involvement in the neuropathology of natural scrapie has not been studied. We assessed the gene expression of ovine TLRs in four anatomically distinct brain regions in natural scrapie-infected sheep and evaluated the possible correlations between gene expression and the pathological hallmarks of prion disease. We observed significant changes in TLR expression in scrapie-infected sheep that correlate with the degree of spongiosis, PrPSc deposition, and gliosis in each of the regions studied. Remarkably, TLR4 was the only gene upregulated in all regions, regardless of the severity of neuropathology. In the hippocampus, we observed milder neuropathology associated with a distinct TLR gene expression profile and the presence of a peculiar microglial morphology, called rod microglia, described here for the first time in the brain of scrapie-infected sheep. The concurrence of these features suggests partial neuroprotection of the hippocampus. Finally, a comparison of the findings in naturallyinfected sheep versus an ovinized mouse model (tg338 mice) revealed distinct patterns of TLRgene expression.

Idioma: Inglés

DOI: 10.3390/ijms23073579

Año: 2022

Publicado en: International Journal of Molecular Sciences 23, 7 (2022), 3579 [24 pp.]
ISSN: 1661-6596

Factor impacto JCR: 5.6 (2022)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 66 / 285 = 0.232 (2022) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 178 = 0.292 (2022) - Q2 - T1

Factor impacto CITESCORE: 7.8 - Biochemistry, Genetics and Molecular Biology (Q1) - Computer Science (Q1) - Chemistry (Q1) - Chemical Engineering (Q1) - Medicine (Q1)

Factor impacto SCIMAGO: 1.154 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/A05-20R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Area Anatom.Embriol.Humana (Dpto. Anatom.Histolog.Humanas)