{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:44:32Z","timestamp":1792640672581,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T00:00:00Z","timestamp":1606003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Italian Ministry of Health","award":["RF-2016-02362195"],"award-info":[{"award-number":["RF-2016-02362195"]}]},{"name":"AICE-FIRE Foundation","award":["RA-101"],"award-info":[{"award-number":["RA-101"]}]},{"name":"AICE-FIRE Foundation","award":["NET-2013-02355313"],"award-info":[{"award-number":["NET-2013-02355313"]}]},{"name":"AICE-FIRE Foundation","award":["EpiCARE 2017-2020"],"award-info":[{"award-number":["EpiCARE 2017-2020"]}]},{"name":"Associazione Paolo Zorzi per le Neuroscienze"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmission and may be critically involved in the pathophysiology of epilepsy. Alterations in dendritic morphology and spine loss mainly in hippocampal neurons have been reported both in epilepsy animal models and in human brain tissues from patients with epilepsy. However, it is still unclear whether these dendritic abnormalities relate to the cause of epilepsy or are generated by seizure recurrence. We investigated fine neuronal structures at the level of dendritic and spine organization using Golgi impregnation, and analysed synaptic networks with immunohistochemical markers of glutamatergic (vGLUT1) and GABAergic (vGAT) axon terminals in human cerebral cortices derived from epilepsy surgery. Specimens were obtained from 28 patients with different neuropathologically defined aetiologies: type Ia and type II focal cortical dysplasia, cryptogenic (no lesion) and temporal lobe epilepsy with hippocampal sclerosis. Autoptic tissues were used for comparison. Three-dimensional reconstructions of Golgi-impregnated neurons revealed severe dendritic reshaping and spine alteration in the core of the type II focal cortical dysplasia. Dysmorphic neurons showed increased dendritic complexity, reduction of dendritic spines and occasional filopodia-like protrusions emerging from the soma. Surprisingly, the intermingled normal-looking pyramidal neurons also showed severe spine loss and simplified dendritic arborization. No changes were observed outside the dysplasia (perilesional tissue) or in neocortical postsurgical tissue obtained in the other patient groups. Immunoreactivities of vGLUT1 and vGAT showed synaptic reorganization in the core of type II dysplasia characterized by the presence of abnormal perisomatic baskets around dysmorphic neurons, in particular those with filopodia-like protrusions, and changes in vGLUT1\/vGAT expression. Ultrastructural data in type II dysplasia highlighted the presence of altered neuropil engulfed by glial processes. Our data indicate that the fine morphological aspect of neurons and dendritic spines are normal in epileptogenic neocortex, with the exception of type II dysplastic lesions. The findings suggest that the mechanisms leading to this severe form of cortical malformation interfere with the normal dendritic arborization and synaptic network organization. The data argue against the concept that long-lasting epilepsy and seizure recurrence per se unavoidably produce a dendritic pathology.<\/jats:p>","DOI":"10.1093\/brain\/awaa387","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T16:39:31Z","timestamp":1603730371000},"page":"251-265","source":"Crossref","is-referenced-by-count":84,"title":["Dendritic pathology, spine loss and synaptic reorganization in human cortex from epilepsy patients"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3571-8779","authenticated-orcid":false,"given":"Laura","family":"Rossini","sequence":"first","affiliation":[{"name":"Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-2067","authenticated-orcid":false,"given":"Dalia","family":"De Santis","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-6603","authenticated-orcid":false,"given":"Roberta Rosa","family":"Mauceri","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Tesoriero","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Bentivoglio","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Maderna","sequence":"additional","affiliation":[{"name":"Division of Neurology V and Neuropathology, Fondazione IRCCS, Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-2520","authenticated-orcid":false,"given":"Antonio","family":"Maiorana","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Deleo","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"de Curtis","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Tringali","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Fondazione IRCCS, Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Cossu","sequence":"additional","affiliation":[{"name":"\u201cClaudio Munari\u201d Epilepsy Surgery Center, GOM Niguarda, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Tumminelli","sequence":"additional","affiliation":[{"name":"\u201cClaudio Munari\u201d Epilepsy Surgery Center, GOM Niguarda, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Bramerio","sequence":"additional","affiliation":[{"name":"Department of Pathology, GOM Niguarda, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Spreafico","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tassi","sequence":"additional","affiliation":[{"name":"\u201cClaudio Munari\u201d Epilepsy Surgery Center, GOM Niguarda, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6475-4974","authenticated-orcid":false,"given":"Rita","family":"Garbelli","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,22]]},"reference":[{"key":"2021021221080268900_awaa387-B1","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00401-019-02061-5","article-title":"Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. 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