{"@type": "dcat:Dataset", "accessLevel": "public", "bureauCode": ["009:25"], "contactPoint": {"@type": "vcard:Contact", "fn": "NIH", "hasEmail": "mailto:info@nih.gov"}, "description": "Background\n          The excitatory amino acid domoic acid, a glutamate and kainic acid analog, is the causative agent of amnesic shellfish poisoning in humans. No studies to our knowledge have investigated the potential contribution to short-term neurotoxicity of the brain microglia, a cell type that constitutes circa 10% of the total glial population in the brain. We tested the hypothesis that a short-term in vitro exposure to domoic acid, might lead to the activation of rat neonatal microglia and the concomitant release of the putative neurotoxic mediators tumor necrosis factor-\u03b1 (TNF-\u03b1), matrix metalloproteinases-2 and-9 (MMP-2 and -9) and superoxide anion (O2-).\n        \n        \n          Results\n          In vitro, domoic acid [10 \u03bcM-1 mM] was significantly neurotoxic to primary cerebellar granule neurons. Although neonatal rat microglia expressed ionotropic glutamate GluR4 receptors, exposure during 6 hours to domoic acid [10 \u03bcM-1 mM] had no significant effect on viability. By four hours, LPS (10 ng/mL) stimulated an increase in TNF-\u03b1 mRNA and a 2,233 % increase in TNF-\u03b1 protein In contrast, domoic acid (1 mM) induced a slight rise in TNF-\u03b1 expression and a 53 % increase (p < 0.01) of immunoreactive TNF-\u03b1 protein. Furthermore, though less potent than LPS, a 4-hour treatment with domoic acid (1 mM) yielded a 757% (p < 0.01) increase in MMP-9 release, but had no effect on MMP-2. Finally, while PMA (phorbol 12-myristate 13-acetate) stimulated O2- generation was elevated in 6 hour LPS-primed microglia, a similar pretreatment with domoic acid (1 mM) did not prime O2- release.\n        \n        \n          Conclusions\n          To our knowledge this is the first experimental evidence that domoic acid, at in vitro concentrations that are toxic to neuronal cells, can trigger a release of statistically significant amounts of TNF-\u03b1 and MMP-9 by brain microglia. These observations are of considerable pathophysiological significance because domoic acid activates rat microglia several days after in vivo administration.", "distribution": [{"@type": "dcat:Distribution", "description": "Visit the original government dataset for complete information, documentation, and data access.", "downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59507/", "mediaType": "text/html", "title": "Official Government Data Source"}], "identifier": "https://healthdata.gov/api/views/43rr-3674", "issued": "2025-07-14", "keyword": ["domoic-acid", "microglia-activation", "neurotoxicity", "nih", "tumor-necrosis-factor"], "landingPage": "https://healthdata.gov/d/43rr-3674", "modified": "2025-09-06", "programCode": ["009:033"], "publisher": {"@type": "org:Organization", "name": "National Institutes of Health"}, "theme": ["NIH"], "title": "Effect of a short-term in vitro exposure to the marine toxin domoic acid on viability, tumor necrosis factor-alpha, matrix metalloproteinase-9 and superoxide anion release by rat neonatal microglia"}