{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:09:56Z","timestamp":1791216596590,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,12,7]],"date-time":"2007-12-07T00:00:00Z","timestamp":1196985600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Tuberous sclerosis complex (TSC) is characterized by brain lesions, epilepsy, increased incidence of mental retardation and autism. The causal link between lesion load and epilepsy on cognitive disabilities has been debated, and these factors explain only part of the intelligence quotient variability. A <jats:italic>Tsc2<\/jats:italic> rat model of the disease provided evidence that the <jats:italic>TSC<\/jats:italic> genes are directly involved in neuronal function. However, these lesion\u2010 and epilepsy\u2010free animals did not show learning deficits, leaving open the possibility that the presence of brain lesions or epilepsy is a prerequisite for the cognitive deficits to fully develop. Here, we reinvestigated the relation among cerebral lesions, epilepsy, and cognitive function using <jats:italic>Tsc1<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used immunocytochemistry and high\u2010resolution magnetic resonance imaging to study the presence of neuronal pathology in <jats:italic>Tsc1<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>mice. We used the Morris water maze, fear conditioning, social interaction, and nest building test to study the presence of cognitive and social deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed no spontaneous seizures or cerebral lesions in the brains of <jats:italic>Tsc1<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>mice. In addition, giant dysmorphic cells were absent, and spine number and dendritic branching appeared to be normal. Nevertheless, <jats:italic>Tsc1<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>mice showed impaired learning in the hippocampus\u2010sensitive versions of the learning tasks and impaired social behavior.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p><jats:italic>Tsc1<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>mice show social and cognitive deficits in the absence of apparent cerebral pathology and spontaneous seizures. These findings support a model in which haploinsufficiency for the <jats:italic>TSC<\/jats:italic> genes leads to aberrations in neuronal functioning resulting in impaired learning and social behavior. Ann Neurol 2007<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21317","type":"journal-article","created":{"date-parts":[[2007,12,7]],"date-time":"2007-12-07T19:16:33Z","timestamp":1197054993000},"page":"648-655","source":"Crossref","is-referenced-by-count":229,"title":["Cognitive deficits in <i>Tsc1<\/i><sup>+\/\u2212<\/sup>mice in the absence of cerebral lesions and seizures"],"prefix":"10.1002","volume":"62","author":[{"given":"Susanna M. I.","family":"Goorden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geeske M.","family":"van Woerden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"van der Weerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P.","family":"Cheadle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ype","family":"Elgersma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291702007092"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01046223"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhj144"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291701004561"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/08830738060210020901"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/08830738040190090501"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01035.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2003.026815"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc062928"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2003.09.003"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1566"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1385\/MN:34:3:205"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.06.003"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04594.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03538.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi190"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/35010550"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5540-06.2007"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0865-8"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02100.x"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.106.2.274"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7319"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15629"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2002.1184"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-004-1038-2"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.2310\/7010.2006.00046"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11413"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0195-70"},{"key":"e_1_2_6_30_2","first-page":"1206","article-title":"Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ\u2010line Tsc2 mutation in mice","volume":"59","author":"Kobayashi T","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.525"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.21317","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.21317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T05:41:18Z","timestamp":1697434878000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.21317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["10.1002\/ana.21317"],"URL":"https:\/\/doi.org\/10.1002\/ana.21317","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12]]}}}