{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:12:50Z","timestamp":1791112370853,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,3,18]],"date-time":"2008-03-18T00:00:00Z","timestamp":1205798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Genetic loss of<jats:italic>TSC1\/TSC2<\/jats:italic>function in tuberous sclerosis complex (TSC) results in overactivation of the mammalian target of rapamycin complex 1 pathway, leading to cellular dysplasia. We hypothesized that the dysplastic cells in TSC tubers are heterogeneous, including separable classes on a neuronal\u2010glial spectrum, and that these dysplastic cells express glutamate receptor (GluR) patterns consistent with increased cortical network excitability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Surgically resected human cortical tubers and nondysplastic epileptic cortical samples were analyzed by double\u2010label immunocytochemistry for coexpression of neuronal and glial markers, the TSC1\/TSC2 pathway downstream molecule phospho\u2010S6 (pS6) and GluR subunits, and compared with control cortical tissue. Western blotting was used to quantify changes in GluR subunit expression in tubers versus controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that cortical tubers contain a broad spectrum of cell types including disoriented pyramidal cells, dysplastic neurons, giant neuroglial cells, dysplastic astroglia, and reactive astrocytes. Dysplastic neurons, giant cells, and dysplastic astroglia express high levels of pS6 and demonstrate altered GluR subunit composition, resembling those of normal immature neurons and glia. In contrast, nondysplastic neurons in TSC and non\u2010TSC epileptic lesions express lower pS6 levels and display changes in GluR subunit expression that are distinct from the patterns seen in tuber dysplastic cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This work significantly expands the spectrum of abnormal cells recognized in tubers beyond the classic tuber giant cell and demonstrates cell\u2010specific abnormalities in GluR expression that may contribute to seizure pathogenesis in TSC. Furthermore, these results suggest that subunit\u2010specific antagonists may be of potential use in the treatment of epilepsy in TSC. 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