{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:05:10Z","timestamp":1790057110038,"version":"4.0.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Synaptic Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Docosahexaenoic acid (DHA), the predominant omega-3 (\u03c9-3) fatty acid in the brain, which contributes to synaptic membrane organization and plasticity, is commonly recommended for brain health. However, \u03c9-3 formulations commonly combine DHA with eicosapentaenoic acid (EPA) in varying proportions, and the impact of the DHA ratio on postsynaptic scaffold regulation remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, differentiated human SH-SY5Y neurons were cultured in the presence of DHA, EPA, or defined DHA ratios (2:1, 1:1, 1:2) at equivalent total concentrations. PSD-95 expression, puncta density, colocalization with the presynaptic marker synaptophysin (SYN), and glutamatergic signaling proteins were quantified by immunofluorescence and Western blot analysis. Metabolic activity was assessed using a colorimetric MTT assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DHA produced the largest increase in PSD-95 protein abundance by immunoblot and the strongest effects on PSD-95 puncta density and SYN colocalization, accompanied by coordinated upregulation of N-methyl-D-aspartate receptor (NMDAR), \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and calcium\/calmodulin-dependent protein kinase II (CaMKII). DHA-enriched compositions preserved this profile, whereas balanced or EPA-dominant compositions showed attenuated responses relative to DHA-dominant conditions. EPA alone failed to enhance postsynaptic scaffold abundance and reduced NMDAR levels relative to control. These effects occurred without a detectable reduction in cellular metabolic activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings demonstrate that the composition of \u03c9-3 fatty acid has a significant bearing on postsynaptic scaffold organization and glutamatergic signaling in differentiated neurons, with DHA serving as the chief mediator of observed effects. This composition-dependent framework provides an experimental basis for considering DHA ratio when evaluating omega-3 effects on postsynaptic protein organization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnsyn.2026.1947075","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:39:00Z","timestamp":1790055540000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DHA-dominant Omega-3 compositions enhance PSD-95 organization and glutamatergic protein expression"],"prefix":"10.3389","volume":"18","author":[{"given":"Gerardo","family":"Medina","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute","place":["Ottawa, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Baird","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute","place":["Ottawa, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia A.","family":"Rodriguez-Alcocer","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute","place":["Ottawa, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex E.","family":"MacKenzie","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute","place":["Ottawa, ON, Canada"]},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa","place":["Ottawa, ON, Canada"]},{"name":"Eric Poulin Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa","place":["Ottawa, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"10858","DOI":"10.1073\/pnas.0502903102","article-title":"Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival","volume":"102","author":"Akbar","year":"2005","journal-title":"Proc. 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