{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:56:40Z","timestamp":1787817400703,"version":"build-2784847793"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["304623\/2025-3"],"award-info":[{"award-number":["304623\/2025-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["406484\/2022-8"],"award-info":[{"award-number":["406484\/2022-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"award":["304623\/2025-3"],"award-info":[{"award-number":["304623\/2025-3"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"award":["406484\/2022-8"],"award-info":[{"award-number":["406484\/2022-8"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Children\u2019s Cancer Institute"},{"name":"Brazilian Federal Agency for Support and Evaluation of Graduate Education"},{"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Center for Advanced Neurology and Neurosurgery"},{"name":"Mackenzie Evangelical University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background: Glutamatergic neuron-to-glioma signaling mediated by \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has emerged as an important mechanism in glioma progression. Objectives\/Methods: We analyzed the expression of the AMPAR subunit genes GRIA1, GRIA2, GRIA3, and GRIA4 in lower-grade glioma (LGG). Results: Expression of GRIA1\u2013GRIA4 was highest in IDH-mutant\/1p19q-codeleted tumors and lowest in IDH-wildtype tumors across both The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. High expression of each GRIA gene was associated with longer overall survival (OS). Transcriptome-wide analyses identified positive correlations between an AMPAR score and genes involved in synaptic organization, neuronal connectivity, and neurotransmission. Co-expression analyses demonstrated coordinated expression between GRIA1\u2013GRIA4 and genes encoding AMPAR auxiliary proteins. Gene Ontology (GO) enrichment revealed overrepresentation of synaptic signaling, trans-synaptic communication, and synapse organization. Although the AMPAR score was associated with favorable survival in univariate analyses, it did not retain independent prognostic significance after adjustment for key clinicomolecular variables. Elevated expression of AMPAR subunit genes in LGG was associated with favorable molecular subtypes and a synaptic transcriptional program. Conclusions: These findings suggest that GRIA1\u2013GRIA4 expression is associated with a synaptically enriched transcriptional program in LGG, although its cellular origin remains uncertain.<\/jats:p>","DOI":"10.3390\/brainsci16080773","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AMPAR Subunit Gene Expression Marks a Synaptic Transcriptional State in Lower-Grade Glioma"],"prefix":"10.3390","volume":"16","author":[{"given":"Bruno","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus","family":"Dalmolin","sequence":"additional","affiliation":[{"name":"InovAI Lab, nPITI\/IMD, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil"},{"name":"Bioinformatics Multidisciplinary Environment (BioME), Federal University of Rio Grande do Norte, Natal 59078-970, Brazil"},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2604-6350","authenticated-orcid":false,"given":"Henrique Ritter","family":"Dal-Pizzol","sequence":"additional","affiliation":[{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre 90035-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo","family":"Malafaia","sequence":"additional","affiliation":[{"name":"Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-2506","authenticated-orcid":false,"given":"Marcelo A. C.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"InovAI Lab, nPITI\/IMD, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil"},{"name":"Bioinformatics Multidisciplinary Environment (BioME), Federal University of Rio Grande do Norte, Natal 59078-970, Brazil"},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"Department of Computer Engineering and Automation, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Munhoz de Paula Alves","family":"Coelho","sequence":"additional","affiliation":[{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"Department of Scientific Development and Innovation (DECIPE), Center for Anatomo-Pathological Diagnosis (CEDAP), Joinville 89200-000, Brazil"},{"name":"Graduate Program in Medicine: Medical Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-2261","authenticated-orcid":false,"given":"Rafael","family":"Roesler","sequence":"additional","affiliation":[{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre 90035-903, Brazil"},{"name":"Graduate Program in Medicine: Medical Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil"},{"name":"Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil"},{"name":"Center for Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo R.","family":"Isolan","sequence":"additional","affiliation":[{"name":"Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, Brazil"},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"The Center for Advanced Neurology and Neurosurgery (CEANNE), Porto Alegre 90560-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/s41586-024-08579-3","article-title":"GABAergic neuron-to-glioma synapses in diffuse midline gliomas","volume":"639","author":"Barron","year":"2025","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.1038\/s41467-024-48757-5","article-title":"Glioblastoma disrupts cortical network activity at multiple spatial and temporal scales","volume":"15","author":"Meyer","year":"2024","journal-title":"Nat. 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