{"doi":"10.1016/j.nbd.2022.105834","title":"Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampus","abstract":"Synapse dysfunction and loss are central features of neurodegenerative diseases, caused in part by the accumulation of protein oligomers. Amyloid-β, tau, prion, and α-synuclein oligomers bind to the cellular prion protein (PrPC), resulting in the activation of macromolecular complexes and signaling at the post-synapse, yet the early signaling events are unclear. Here we sought to determine the early transcript and protein alterations in the hippocampus during the pre-clinical stages of prion disease. We used a transcriptomic approach focused on the early-stage, prion-infected hippocampus of male wild-type mice, and identify immediate early genes, including the synaptic activity response gene, Arc/Arg3.1, as significantly upregulated. In a longitudinal study of male, prion-infected mice, Arc/Arg-3.1 protein was increased early (40% of the incubation period), and by mid-disease (pre-clinical), phosphorylated AMPA receptors (pGluA1-S845) were increased and metabotropic glutamate receptors (mGluR5 dimers) were markedly reduced in the hippocampus. Notably, sporadic Creutzfeldt-Jakob disease (sCJD) post-mortem cortical samples also showed low levels of mGluR5 dimers. Together, these findings suggest that prions trigger an early Arc response, followed by an increase in phosphorylated GluA1 and a reduction in mGluR5 receptors.","journal":"Neurobiology of Disease","year":2022,"id":261150,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":335160,"name":"Jessica Lawrence","orcid":"0000-0002-8315-1909","position":1,"is_corresponding":false},{"id":335948,"name":"Katrin Soldau","orcid":null,"position":2,"is_corresponding":false},{"id":335161,"name":"Donald Pizzo","orcid":"0000-0002-8022-3604","position":3,"is_corresponding":false},{"id":284761,"name":"Emily C. Wheeler","orcid":"0000-0003-0260-8530","position":4,"is_corresponding":false},{"id":335947,"name":"Patricia Aguilar‐Calvo","orcid":null,"position":5,"is_corresponding":false},{"id":915969,"name":"Helen Khuu","orcid":null,"position":6,"is_corresponding":false},{"id":915353,"name":"Joy Chen","orcid":"0000-0002-1318-1766","position":7,"is_corresponding":false},{"id":915354,"name":"Adela Malik","orcid":"0000-0001-6827-3935","position":8,"is_corresponding":false},{"id":915970,"name":"Gail Funk","orcid":null,"position":9,"is_corresponding":false},{"id":915355,"name":"Percival Nam","orcid":"0000-0002-6577-589X","position":10,"is_corresponding":false},{"id":915971,"name":"Henry Sánchez","orcid":null,"position":11,"is_corresponding":false},{"id":347892,"name":"Michael D. Geschwind","orcid":"0000-0003-2861-3776","position":12,"is_corresponding":false},{"id":524160,"name":"Chengbiao Wu","orcid":"0000-0002-3660-088X","position":13,"is_corresponding":false},{"id":43290,"name":"G Yeo","orcid":null,"position":14,"is_corresponding":false},{"id":281403,"name":"Xu Chen","orcid":"0000-0001-8926-3090","position":15,"is_corresponding":false},{"id":774792,"name":"Gentry N. Patrick","orcid":"0000-0001-6405-4401","position":16,"is_corresponding":false},{"id":335166,"name":"Christina J. Sigurdson","orcid":"0000-0002-1770-0965","position":17,"is_corresponding":false},{"id":366782,"name":"Daniel Ojeda-Juárez","orcid":"0000-0002-0722-2509","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T00:26:12.158801Z","pmid":"35905927","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}