{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T13:46:22Z","timestamp":1762955182228,"version":"3.45.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201013\u2010JSV4\u20100006"],"award-info":[{"award-number":["ANR\u201013\u2010JSV4\u20100006"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001673","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Mutations in genes of the mTOR pathway have been identified as a major cause of hemimegalencephaly (HMG), focal cortical dysplasia type II, and tuberous sclerosis, cortical malformations associated with epilepsy. These conditions are characterized at the cellular level by increased size of pyramidal neurons that grow with dysmorphic features and in some cases by the presence of giant balloon cells. Our previous research in tuberous sclerosis has shown that parvalbumin (Pvalb) and calbindin immunoreactive cells in cortical and subcortical tuberal lesions show cytomegalic features, suggesting the involvement of GABAergic cells in mTOR\u2010related pathologies. In the present report, we propose to deepen our understanding of the role of interneurons in mTOR\u2010related cortical malformations by analyzing the maturation of Pvalb neurons in fetal samples of HMG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed immunohistochemical staining of cortical samples from individuals with HMG from 21 gestational weeks to 10 postnatal months. The study focused on Pvalb cells, and pS6 counterstaining was performed to assess the activation of the mTOR pathway. To investigate the pathomechanisms behind the cytomegalic features, we examined mTOR pathway gene expression in Pvalb interneurons and cortical projection neurons using a single\u2010cell transcriptomic atlas of the human neocortex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results revealed cytomegalic features in Pvalb interneurons, indicating abnormal development in HMG patients compared to controls. This phenotype progressively worsened over time, suggesting ongoing developmental abnormalities associated with mTOR dysregulation, which may underlie the pathology of cortical malformations in HMG. Our transcriptomic data revealed similar expression patterns of mTOR and its upstream regulators in both Pvalb and glutamatergic neurons during development, suggesting that mTOR pathway disorders may induce similar phenotypes in both cell types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The present data suggest that Pvalb interneurons are involved in the development of mTOR\u2010related cortical dysplasia and that they may be a contributor to the clinical phenotype of these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18325","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T04:49:57Z","timestamp":1740026997000},"page":"2099-2109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cytomegalic parvalbumin neurons in fetal cases of hemimegalencephaly"],"prefix":"10.1111","volume":"66","author":[{"given":"Antoinette\u2010Bernabe","family":"Gelot","sequence":"first","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"},{"name":"Neuropathology, H\u00f4pital Trousseau, Assistance Publique\u2010H\u00f4pitaux Parisiens Sorbonne Universit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tangra Ondina","family":"Draia\u2010Nicolau","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9mi","family":"Mathieu","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Silvagnoli","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Watrin","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Cardoso","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2436-8593","authenticated-orcid":false,"given":"Jean\u2010Bernard","family":"Manent","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"de Chevigny","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5096-8939","authenticated-orcid":false,"given":"Alfonso","family":"Represa","sequence":"additional","affiliation":[{"name":"INMED, INSERM Aix\u2010Marseille University  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02061-5"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24357"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31736"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12377"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac117"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106144"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0251-0"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022392"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13200"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17301"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0395-6"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00899"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0257-3"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm175"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-016-9142-0"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111085"},{"key":"e_1_2_13_18_1","doi-asserted-by":"crossref","unstructured":"BaulacS BaldassariS KlinglerE TeijeiroLG DoladilheM RaouxC et\u00a0al.Single\u2010cell genotyping and transcriptomic profiling in focal cortical dysplasia [Internet]. 2024 [cit\u00e9 2024]. 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