{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:07:04Z","timestamp":1773414424590,"version":"3.50.1"},"reference-count":378,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The ontological categorization of the cellular elements of the brain was proposed over a century ago by Santiago Ram\u00f3n y Cajal (neurons, astroglia) and P\u00edo del R\u00edo-Hortega (oligodendroglia, microglia). It combines histochemical observations of morphology with allied inferences about the specialized functions and origins (ectoderm or mesoderm) of each cellular element. This ontology shapes modern neuroscience, with the main non-neuronal cells\u2014astroglia, oligodendroglia and microglia\u2014viewed as having distinct primary roles relating respectively to the metabolic support, myelination and immunoprotection of neurons, the information signaling cells. Yet contemporary techniques, ranging from electrophysiology to single-cell transcriptomics and ultrahigh resolution spectroscopy, are revealing intersecting molecular profiles and functional capacities of these cell groups, for example metabolic support, neuroimmune and signaling functions in oligodendroglia. Here we identify discrepancies in current glial paradigms, from empirical, evolutionary and pragmatic perspectives. We suggest a subset of small, iron-rich glial cells, usually with few processes, often viewed as oligodendroglia with myelin-related primary functions, instead have iron-related primary functions that are central to all aspects of brain activity. We call these \u2018ferriglia\u2019. We discuss implications for pathogenesis across the spectrum of neuropsychiatric and neurological disorders, including neurodegenerative conditions such as Alzheimer\u2019s disease and other less common cognitive, movement and neurobehavioral disorders, stroke and cerebrovascular disease, glioblastoma and other brain cancers and neuroimmune conditions. We also briefly address the question of where ferriglia may reside within existing glial compartments and lineages, implications for the ontological classification of other glial cells, and research challenges that must be overcome going forward.<\/jats:p>","DOI":"10.3390\/cells15060511","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:12:25Z","timestamp":1773400345000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paradoxes in the Ontological Classification of Glia\u2014Evidence for an Important New Class of Brain Cells with Primary Functions in Iron Regulation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-7795","authenticated-orcid":false,"given":"Adrienne E.","family":"Milward","sequence":"first","affiliation":[{"name":"Faculty of Science, Medicine and Health, School of Medical, Health and Indigenous Sciences, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"The Florey Institute, University of Melbourne, Parkville, VIC 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-4883","authenticated-orcid":false,"given":"Rebecca J.","family":"Hood","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, School of Biomedicine, University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan-An","family":"Lin","sequence":"additional","affiliation":[{"name":"Faculty of Science, Medicine and Health, School of Medical, Health and Indigenous Sciences, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9090-7690","authenticated-orcid":false,"given":"Concei\u00e7\u00e3o","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvis","family":"Acquah","sequence":"additional","affiliation":[{"name":"Department of Pathology, ARUP Institute of Clinical & Experimental Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jake","family":"Brooks","sequence":"additional","affiliation":[{"name":"The Biomedical Engineering Institute, School of Engineering, Faculty of Science, Engineering and Medicine, University of Warwick, Coventry, CV4 7AL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-4183","authenticated-orcid":false,"given":"Joanna F.","family":"Collingwood","sequence":"additional","affiliation":[{"name":"The Biomedical Engineering Institute, School of Engineering, Faculty of Science, Engineering and Medicine, University of Warwick, Coventry, CV4 7AL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-7905","authenticated-orcid":false,"given":"Yoshiteru","family":"Kagawa","sequence":"additional","affiliation":[{"name":"The Florey Institute, University of Melbourne, Parkville, VIC 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1708-9430","authenticated-orcid":false,"given":"Samantha J.","family":"Richardson","sequence":"additional","affiliation":[{"name":"School of Science, STEM College, RMIT University, Melbourne, VIC 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3196-5916","authenticated-orcid":false,"given":"Yuting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1221-6709","authenticated-orcid":false,"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0598-4195","authenticated-orcid":false,"given":"Mirella","family":"Dottori","sequence":"additional","affiliation":[{"name":"Faculty of Science, Medicine and Health, School of Medical, Health and Indigenous Sciences, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel M.","family":"Johnstone","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","unstructured":"Burkhardt, F., and Smith, S. 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