{"doi":"10.1371/journal.pbio.3002308","title":"Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing","abstract":"Hyperglycemia increases glucose concentrations in the cerebrospinal fluid (CSF), activating glucose-sensing mechanisms and feeding behavior in the hypothalamus. Here, we discuss how hyperglycemia temporarily modifies ependymal cell ciliary beating to increase hypothalamic glucose sensing. A high level of glucose in the rat CSF stimulates glucose transporter 2 (GLUT2)-positive subcommissural organ (SCO) cells to release SCO-spondin into the dorsal third ventricle. Genetic inactivation of mice GLUT2 decreases hyperglycemia-induced SCO-spondin secretion. In addition, SCO cells secrete Wnt5a-positive vesicles; thus, Wnt5a and SCO-spondin are found at the apex of dorsal ependymal cilia to regulate ciliary beating. Frizzled-2 and ROR2 receptors, as well as specific proteoglycans, such as glypican/testican (essential for the interaction of Wnt5a with its receptors) and Cx43 coupling, were also analyzed in ependymal cells. Finally, we propose that the SCO-spondin/Wnt5a/Frizzled-2/Cx43 axis in ependymal cells regulates ciliary beating, a cyclic and adaptive signaling mechanism to control glucose sensing.","journal":"PLoS Biology","year":2023,"id":350125,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1094035,"name":"Manuel Cifuentes","orcid":"0000-0003-1414-469X","position":1,"is_corresponding":false},{"id":1094036,"name":"Eder Ramírez","orcid":"0000-0002-1050-7636","position":2,"is_corresponding":false},{"id":1094037,"name":"Fernando Martínez de Juan","orcid":"0000-0003-1554-7861","position":3,"is_corresponding":false},{"id":1094038,"name":"María José Barahona","orcid":"0009-0007-3051-4036","position":4,"is_corresponding":false},{"id":1094039,"name":"Luciano Ferrada","orcid":"0000-0001-5478-2325","position":5,"is_corresponding":false},{"id":1094617,"name":"Natalia Saldivia","orcid":null,"position":6,"is_corresponding":false},{"id":305928,"name":"Ernesto R. Bongarzone","orcid":"0000-0003-1664-6634","position":7,"is_corresponding":false},{"id":660516,"name":"Bernard Thorens","orcid":"0000-0002-3738-0129","position":8,"is_corresponding":false},{"id":1094040,"name":"Katterine Salazar","orcid":"0000-0002-1518-1217","position":9,"is_corresponding":false},{"id":1094034,"name":"Francisco Nualart","orcid":"0000-0002-7762-1417","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:12:23.769679Z","pmid":"37733692","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":[]}