{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T15:07:58Z","timestamp":1740150478829,"version":"3.37.3"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"DOD TSCRP Idea Development","award":["W81XWH-15-1-0112","K08-NS048064"],"award-info":[{"award-number":["W81XWH-15-1-0112","K08-NS048064"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001771","name":"Tuberous Sclerosis Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001771","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DOD TSCRP Idea Development","award":["W81XWH-16-1-0263","W81XWH-15-1-0112","K01 MH096956"],"award-info":[{"award-number":["W81XWH-16-1-0263","W81XWH-15-1-0112","K01 MH096956"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cytomegalic neurons, characterized by increased size and a hyperactive mechanistic target of rapamycin complex 1 (mTORC1), are pathognomonic for tuberous sclerosis complex (TSC). To model these neurons, we recently generated a murine Tsc1 conditional knockout model in which Tsc1 deletion in late embryonic radial glia results in neuronal hypertrophy of a subset of isocortical pyramidal neurons. In the current study, we compared the cellular pathology of these cytomegalic neurons to those of the enlarged neurons in human cortical tubers. Neurons from the mice showed unique features, such as cytoplasmic vacuoles associated with Golgi complexes and the ectopic formation of perineuronal nets (PNNs), a feature of inhibitory neurons, rarely present in excitatory cortical neurons. The membranes of these vacuoles were enriched for the plasma membrane proteins CD44, KCC2, and Na+\/K+ ATPase, suggesting deficits in Golgi membrane trafficking. These aberrant features in the mouse appeared only after the onset of seizures, probably due to the prolonged seizure activity in the context of constitutive mTORC1 activation. Similar PNNs and cytoplasmic vacuoles were present in the cytomegalic neurons of human cortical tubers. Our findings reveal novel pathological features of Golgi complexes and PNNs in the cytomegalic neurons in TSC.<\/jats:p>","DOI":"10.1093\/jnen\/nlae079","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T17:31:52Z","timestamp":1721323912000},"page":"1047-1059","source":"Crossref","is-referenced-by-count":0,"title":["Cytoplasmic vacuolization and ectopic formation of perineuronal nets are characteristic pathologies of cytomegalic neurons in tuberous sclerosis"],"prefix":"10.1093","volume":"83","author":[{"given":"Alexander A","family":"Sosunov","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Columbia University Irving Medical Center , New York, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"McKhann, II","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Columbia University Irving Medical Center , New York, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guomei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University Irving Medical Center , New York, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2135-8936","authenticated-orcid":false,"given":"James E","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center , New York, NY,","place":["United States"]},{"name":"The Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University Irving Medical Center , New York, NY,","place":["United 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