Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization
IntroductionFocal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multic...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1023950/full |
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| author | Guilherme Rossi Assis-Mendonça Guilherme Rossi Assis-Mendonça Maria Carolina Pedro Athié Maria Carolina Pedro Athié João Vitor Gerdulli Tamanini João Vitor Gerdulli Tamanini Arethusa de Souza Arethusa de Souza Gabriel Gerardini Zanetti Gabriel Gerardini Zanetti Patrícia Aline Oliveira Ribeiro de Aguiar Araújo Patrícia Aline Oliveira Ribeiro de Aguiar Araújo Enrico Ghizoni Enrico Ghizoni Helder Tedeschi Helder Tedeschi Marina Koutsodontis Machado Alvim Marina Koutsodontis Machado Alvim Vanessa Simão de Almeida Vanessa Simão de Almeida Welliton de Souza Welliton de Souza Roland Coras Clarissa Lin Yasuda Clarissa Lin Yasuda Ingmar Blümcke André Schwambach Vieira André Schwambach Vieira Fernando Cendes Fernando Cendes Iscia Lopes-Cendes Iscia Lopes-Cendes Fabio Rogerio Fabio Rogerio |
| author_facet | Guilherme Rossi Assis-Mendonça Guilherme Rossi Assis-Mendonça Maria Carolina Pedro Athié Maria Carolina Pedro Athié João Vitor Gerdulli Tamanini João Vitor Gerdulli Tamanini Arethusa de Souza Arethusa de Souza Gabriel Gerardini Zanetti Gabriel Gerardini Zanetti Patrícia Aline Oliveira Ribeiro de Aguiar Araújo Patrícia Aline Oliveira Ribeiro de Aguiar Araújo Enrico Ghizoni Enrico Ghizoni Helder Tedeschi Helder Tedeschi Marina Koutsodontis Machado Alvim Marina Koutsodontis Machado Alvim Vanessa Simão de Almeida Vanessa Simão de Almeida Welliton de Souza Welliton de Souza Roland Coras Clarissa Lin Yasuda Clarissa Lin Yasuda Ingmar Blümcke André Schwambach Vieira André Schwambach Vieira Fernando Cendes Fernando Cendes Iscia Lopes-Cendes Iscia Lopes-Cendes Fabio Rogerio Fabio Rogerio |
| author_sort | Guilherme Rossi Assis-Mendonça |
| collection | DOAJ |
| description | IntroductionFocal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization.MethodsWe investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses.ResultsWe found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells.DiscussionOverall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively. |
| first_indexed | 2024-04-10T00:27:16Z |
| format | Article |
| id | doaj.art-07962596e794421e970f3a49e21d22fa |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-10T00:27:16Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj.art-07962596e794421e970f3a49e21d22fa2023-03-15T05:56:02ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-03-011410.3389/fneur.2023.10239501023950Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterizationGuilherme Rossi Assis-Mendonça0Guilherme Rossi Assis-Mendonça1Maria Carolina Pedro Athié2Maria Carolina Pedro Athié3João Vitor Gerdulli Tamanini4João Vitor Gerdulli Tamanini5Arethusa de Souza6Arethusa de Souza7Gabriel Gerardini Zanetti8Gabriel Gerardini Zanetti9Patrícia Aline Oliveira Ribeiro de Aguiar Araújo10Patrícia Aline Oliveira Ribeiro de Aguiar Araújo11Enrico Ghizoni12Enrico Ghizoni13Helder Tedeschi14Helder Tedeschi15Marina Koutsodontis Machado Alvim16Marina Koutsodontis Machado Alvim17Vanessa Simão de Almeida18Vanessa Simão de Almeida19Welliton de Souza20Welliton de Souza21Roland Coras22Clarissa Lin Yasuda23Clarissa Lin Yasuda24Ingmar Blümcke25André Schwambach Vieira26André Schwambach Vieira27Fernando Cendes28Fernando Cendes29Iscia Lopes-Cendes30Iscia Lopes-Cendes31Fabio Rogerio32Fabio Rogerio33Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Neuropathology, University Hospital Erlangen, Erlangen, GermanyThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Neuropathology, University Hospital Erlangen, Erlangen, GermanyThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, BrazilIntroductionFocal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization.MethodsWe investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses.ResultsWe found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells.DiscussionOverall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively.https://www.frontiersin.org/articles/10.3389/fneur.2023.1023950/fullfocal cortical dysplasiatranscriptomecholesterol biosynthesis enzymeshumanin-like 12GPNMBmolecular biomarker |
| spellingShingle | Guilherme Rossi Assis-Mendonça Guilherme Rossi Assis-Mendonça Maria Carolina Pedro Athié Maria Carolina Pedro Athié João Vitor Gerdulli Tamanini João Vitor Gerdulli Tamanini Arethusa de Souza Arethusa de Souza Gabriel Gerardini Zanetti Gabriel Gerardini Zanetti Patrícia Aline Oliveira Ribeiro de Aguiar Araújo Patrícia Aline Oliveira Ribeiro de Aguiar Araújo Enrico Ghizoni Enrico Ghizoni Helder Tedeschi Helder Tedeschi Marina Koutsodontis Machado Alvim Marina Koutsodontis Machado Alvim Vanessa Simão de Almeida Vanessa Simão de Almeida Welliton de Souza Welliton de Souza Roland Coras Clarissa Lin Yasuda Clarissa Lin Yasuda Ingmar Blümcke André Schwambach Vieira André Schwambach Vieira Fernando Cendes Fernando Cendes Iscia Lopes-Cendes Iscia Lopes-Cendes Fabio Rogerio Fabio Rogerio Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization Frontiers in Neurology focal cortical dysplasia transcriptome cholesterol biosynthesis enzymes humanin-like 12 GPNMB molecular biomarker |
| title | Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization |
| title_full | Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization |
| title_fullStr | Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization |
| title_full_unstemmed | Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization |
| title_short | Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization |
| title_sort | transcriptome analyses of the cortex and white matter of focal cortical dysplasia type ii insights into pathophysiology and tissue characterization |
| topic | focal cortical dysplasia transcriptome cholesterol biosynthesis enzymes humanin-like 12 GPNMB molecular biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1023950/full |
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