{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:05:17Z","timestamp":1753891517139,"version":"3.41.2"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>Prion diseases, such as scrapie, entail the accumulation of disease-specific prion protein (<jats:italic>PrP<\/jats:italic><jats:sup><jats:italic>Sc<\/jats:italic><\/jats:sup>) within the brain. Toll-like receptors (TLRs) are crucial components of the pattern recognition system. They recognize pathogen-associated molecular patterns (PAMPs) and play a central role in orchestrating host innate immune responses. The expression levels of Toll-like receptors (TLRs) in the central nervous system (CNS) were not well-defined. To establish a model of prion diseases in BALB\/C mice, the 22L strain was employed. The features of the 22L strain were analyzed, and the cerebellum exhibited severe pathological changes. TLR1-13 levels in the cerebellum were measured using quantitative polymerase chain reaction (qPCR) at time points of 60, 90, 120, and the final end point (145 days post-infection). During the pathogenesis, the expression levels of Toll-like receptors (TLRs) 1, 2, 7, 8, and 9 increased in a time-dependent manner. This trend mirrored the expression patterns of <jats:italic>PrP<\/jats:italic><jats:sup><jats:italic>Sc<\/jats:italic><\/jats:sup> (the pathological isoform of the prion protein) and glial fibrillary acidic protein. Notably, at the end point, TLR1-13 levels were significantly elevated. Protein level of TLR7 and TLR9 showed increasing at the end point of the 22L-infected mice. A deeper understanding of the increased Toll-like receptors (TLRs) in prion diseases could shed light on their role in initiating immune responses at various stages during pathogenesis. This insight is particularly relevant when considering TLRs as potential therapeutic targets for prion diseases.<\/jats:p>","DOI":"10.3389\/fnbeh.2024.1341901","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T05:06:40Z","timestamp":1713416800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression of Toll-like receptors in the cerebellum during pathogenesis of prion disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Xiangyu","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wufei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyu","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wensen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwei","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.3390\/ani11030691","article-title":"Classical and atypical scrapie in sheep and goats. review on the etiology, genetic factors, pathogenesis, diagnosis, and control measures of both diseases","volume":"11","author":"Ac\u00edn","year":"2021","journal-title":"Animals"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.1007\/s10072-022-05927-x","article-title":"First familial cases of p102l Gerstmann\u2013Str\u00e4ussler\u2013Scheinker syndrome in South Korea: diffusion-weighted imaging might reflect intrafamilial phenotypic variability","volume":"43","author":"Ahn","year":"2022","journal-title":"Neurol. Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"s7","DOI":"10.5530\/ijper.57.1s.2","article-title":"Transmissible spongiform encephalopathy and its regulations","volume":"57","author":"Balamuralidhara","year":"2023","journal-title":"Ind. J. Pharm. Edu. Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.3389\/fimmu.2020.01588","article-title":"Role of toll like receptor 4 in Alzheimer's disease","volume":"11","author":"Calvo-Rodriguez","year":"2020","journal-title":"Front. Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0208559","DOI":"10.1371\/journal.pone.0208559","article-title":"Toll-like receptor 2 confers partial neuroprotection during prion disease","volume":"13","author":"Carroll","year":"2018","journal-title":"PLoS ONE"},{"key":"B6","doi-asserted-by":"publisher","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4909","DOI":"10.1007\/s00415-022-11135-6","article-title":"Proposal of new diagnostic criteria for fatal familial insomnia","volume":"269","author":"Chu","year":"2022","journal-title":"J. Neurol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1006\/bbrc.1999.1730","article-title":"New insight into abnormal prion protein using monoclonal antibodies","volume":"265","author":"Demart","year":"1999","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"B9","doi-asserted-by":"publisher","first-page":"812774","DOI":"10.3389\/fimmu.2022.812774","article-title":"Toll-like receptor signaling and its role in cell-mediated immunity","volume":"13","author":"Duan","year":"2022","journal-title":"Front. Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3389\/fncel.2018.00329","article-title":"Role of microglia TLRs in neurodegeneration","volume":"12","author":"Fiebich","year":"2018","journal-title":"Front. Cell. Neurosci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3579","DOI":"10.3390\/ijms23073579","article-title":"Distinctive toll-like receptors gene expression and glial response in different brain regions of natural scrapie","volume":"23","author":"Garc\u00eda-Mart\u00ednez","year":"2022","journal-title":"Int. J. Mol. Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1150775","article-title":"Lymphatic vasculature in the central nervous system","author":"Gonz\u00e1lez-Hern\u00e1ndez","year":"2023","journal-title":"Front. Cell Dev. Biol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S1474-4422(20)30477-4","article-title":"Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease","volume":"20","author":"Hermann","year":"2021","journal-title":"Lancet Neurol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"230","DOI":"10.18502\/ijaai.v18i3.1117","article-title":"The toll-like receptor 2 (TLR2)-related immunopathological responses in the multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"18","author":"Jafarzadeh","year":"2019","journal-title":"Iran. J. Allergy Asthma Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-022-02378-1","article-title":"Immunological status of the olfactory bulb in a murine model of toll-like receptor 3-mediated upper respiratory tract inflammation","volume":"19","author":"Kagoya","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1010782","DOI":"10.1371\/journal.pgen.1010782","article-title":"Steroid hormone regulation of innate immunity in drosophila melanogaster","volume":"19","author":"Keith","year":"2023","journal-title":"PLoS Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13041-020-0551-3","article-title":"Core transcriptional regulatory circuits in prion diseases","volume":"13","author":"Kim","year":"2020","journal-title":"Mol. Brain"},{"key":"B18","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3390\/biom13010019","article-title":"Differential gene expression induced by different TLR agonists in a549 lung epithelial cells is modulated by CRISPR activation of TLR10","volume":"13","author":"Knez","year":"2022","journal-title":"Biomolecules"},{"key":"B19","doi-asserted-by":"publisher","first-page":"611","DOI":"10.3390\/molecules27030611","article-title":"Prion strains differ in susceptibility to photodynamic oxidation","volume":"27","author":"Kostelanska","year":"2022","journal-title":"Molecules"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e51708","DOI":"10.7759\/cureus.51708","article-title":"Kuru disease: bridging the gap between prion biology and human health","volume":"16","author":"Kothekar","year":"2024","journal-title":"Cureus"},{"key":"B21","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1146\/annurev-med-050715-104343","article-title":"Innate immunity and neurodegeneration","volume":"69","author":"Labzin","year":"2018","journal-title":"Annu. Rev. Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.3390\/ijms22042196","article-title":"Neuroinflammation in prion disease","volume":"22","author":"Li","year":"2021","journal-title":"Int. J. Mol. Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.fsi.2022.04.010","article-title":"Fish-specific toll-like receptor 14 (TLR14) from Asian swamp eel (Monopterus albus) is involved in immune response to bacterial infection","volume":"124","author":"Liu","year":"2022","journal-title":"Fish Shellfish Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1093\/hmg\/ddw108","article-title":"Identification of new molecular alterations in fatal familial insomnia","volume":"25","author":"Llorens","year":"2016","journal-title":"Hum. Mol. Genet"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1988.tb00892.x","article-title":"Immunostaining of scrapie cerebral amyloid plaques with antisera raised to scrapie\u2013associated fibrils (SAF)","author":"McBride","year":"1988","journal-title":"Neuropathol. Appl. Neurobiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.immuni.2020.04.004","article-title":"Nucleic acid sensors as therapeutic targets for human disease","volume":"53","author":"McWhirter","year":"2022","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1177\/1040638718825290","article-title":"Raccoons accumulate PrPSc after intracranial inoculation with the agents of chronic wasting disease (CWD) or transmissible mink encephalopathy (TME) but not atypical scrapie","volume":"31","author":"Moore","year":"2019","journal-title":"J. Vet. Diag. Invest"},{"key":"B28","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.tig.2021.09.006","article-title":"The toll gene in drosophila pattern formation","volume":"38","author":"N\u00fcsslein-Volhard","year":"2022","journal-title":"Trends Genet"},{"key":"B29","doi-asserted-by":"publisher","first-page":"918883","DOI":"10.3389\/fncel.2022.918883","article-title":"Innate immune tolerance in microglia does not impact on central nervous system prion disease","volume":"16","author":"Pal","year":"2022","journal-title":"Front. Cell. Neurosci"},{"key":"B30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-1-4939-7211-1_5","article-title":"\u201cNeuropathology, immunohistochemistry, and biochemistry in human prion diseases,\u201d","volume-title":"Prion Diseases","author":"Ritchie","year":"2017"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1157023","DOI":"10.1155\/2021\/1157023","article-title":"Toll-like receptors (TLRs): structure, functions, signaling, and role of their polymorphisms in colorectal cancer susceptibility","volume":"2021","author":"Sameer","year":"2021","journal-title":"Biomed. Res. Int"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e20202715","DOI":"10.1084\/jem.20202715","article-title":"Functional immune cell-astrocyte interactions","volume":"218","author":"Sanmarco","year":"2021","journal-title":"J. Exp. Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"12474","DOI":"10.1021\/acsomega.2c00155","article-title":"Chronic wasting disease (CWD) in cervids and the consequences of a mutable protein conformation","volume":"7","author":"Silva","year":"2022","journal-title":"ACS Omega"},{"key":"B34","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.bbi.2016.05.016","article-title":"Reprint of: microglial toll-like receptors and Alzheimer's disease","volume":"55","author":"Su","year":"2016","journal-title":"Brain Behav. Immun"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1128\/JVI.75.3.1408-1413.2001","article-title":"Identification of two prion protein regions that modify scrapie incubation time","volume":"75","author":"Supattapone","year":"2001","journal-title":"J. Virol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13195-020-00755-7","article-title":"Associations of Alzheimer's disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration","volume":"13","author":"Tan","year":"2021","journal-title":"Alzheimers. Res. Ther"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1044721","DOI":"10.3389\/fimmu.2022.1044721","article-title":"Antiviral response within different cell types of the CNS","volume":"13","author":"Telikani","year":"2022","journal-title":"Front. Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e12854","DOI":"10.1111\/sji.12854","article-title":"Expression and functions of cellular prion proteins in immunocytes","volume":"91","author":"Zhang","year":"2020","journal-title":"Scand. J. Immunol"}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2024.1341901\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T05:06:44Z","timestamp":1713416804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2024.1341901\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":38,"alternative-id":["10.3389\/fnbeh.2024.1341901"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2024.1341901","relation":{},"ISSN":["1662-5153"],"issn-type":[{"type":"electronic","value":"1662-5153"}],"subject":[],"published":{"date-parts":[[2024,4,18]]},"article-number":"1341901"}}