Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients
Schizophrenia (SZ) is a severe mental disorder that arises from abnormal neurodevelopment, caused by genetic and environmental factors. SZ often involves distortions in reality perception and it is widely associated with alterations in brain connectivity. In the present work, we used Human Induced P...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.935360/full |
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| author | Sofía Puvogel Sofía Puvogel Kris Blanchard Kris Blanchard Bárbara S. Casas Robyn L. Miller Robyn L. Miller Delia Garrido-Jara Sebastián Arizabalos Stevens K. Rehen Magdalena Sanhueza Verónica Palma |
| author_facet | Sofía Puvogel Sofía Puvogel Kris Blanchard Kris Blanchard Bárbara S. Casas Robyn L. Miller Robyn L. Miller Delia Garrido-Jara Sebastián Arizabalos Stevens K. Rehen Magdalena Sanhueza Verónica Palma |
| author_sort | Sofía Puvogel |
| collection | DOAJ |
| description | Schizophrenia (SZ) is a severe mental disorder that arises from abnormal neurodevelopment, caused by genetic and environmental factors. SZ often involves distortions in reality perception and it is widely associated with alterations in brain connectivity. In the present work, we used Human Induced Pluripotent Stem Cells (hiPSCs)-derived neuronal cultures to study neural communicational dynamics during early development in SZ. We conducted gene and protein expression profiling, calcium imaging recordings, and applied a mathematical model to quantify the dynamism of functional connectivity (FC) in hiPSCs-derived neuronal networks. Along the neurodifferentiation process, SZ networks displayed altered gene expression of the glutamate receptor-related proteins HOMER1 and GRIN1 compared to healthy control (HC) networks, suggesting a possible tendency to develop hyperexcitability. Resting-state FC in neuronal networks derived from HC and SZ patients emerged as a dynamic phenomenon exhibiting connectivity configurations reoccurring in time (hub states). Compared to HC, SZ networks were less thorough in exploring different FC configurations, changed configurations less often, presented a reduced repertoire of hub states and spent longer uninterrupted time intervals in this less diverse universe of hubs. Our results suggest that alterations in the communicational dynamics of SZ emerging neuronal networks might contribute to the previously described brain FC anomalies in SZ patients, by compromising the ability of their neuronal networks for rapid and efficient reorganization through different activity patterns. |
| first_indexed | 2024-04-11T21:27:25Z |
| format | Article |
| id | doaj.art-303e2ade3fe840b6b2a7e4033bdd13ed |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T21:27:25Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-303e2ade3fe840b6b2a7e4033bdd13ed2022-12-22T04:02:21ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-09-011010.3389/fcell.2022.935360935360Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patientsSofía Puvogel0Sofía Puvogel1Kris Blanchard2Kris Blanchard3Bárbara S. Casas4Robyn L. Miller5Robyn L. Miller6Delia Garrido-Jara7Sebastián Arizabalos8Stevens K. Rehen9Magdalena Sanhueza10Verónica Palma11Laboratory of Stem Cells and Developmental Biology, Department of Biology, Faculty of Sciences. Universidad de Chile. Santiago, ChileCell Physiology Laboratory, Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileLaboratory of Stem Cells and Developmental Biology, Department of Biology, Faculty of Sciences. Universidad de Chile. Santiago, ChileCell Physiology Laboratory, Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileLaboratory of Stem Cells and Developmental Biology, Department of Biology, Faculty of Sciences. Universidad de Chile. Santiago, ChileDepartment of Computer Science, Georgia State University, Atlanta, GA, United StatesTri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS Center), Atlanta, GA, United StatesLaboratory of Stem Cells and Developmental Biology, Department of Biology, Faculty of Sciences. Universidad de Chile. Santiago, ChileLaboratory of Stem Cells and Developmental Biology, Department of Biology, Faculty of Sciences. Universidad de Chile. Santiago, ChileInstituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, BrazilCell Physiology Laboratory, Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileLaboratory of Stem Cells and Developmental Biology, Department of Biology, Faculty of Sciences. Universidad de Chile. Santiago, ChileSchizophrenia (SZ) is a severe mental disorder that arises from abnormal neurodevelopment, caused by genetic and environmental factors. SZ often involves distortions in reality perception and it is widely associated with alterations in brain connectivity. In the present work, we used Human Induced Pluripotent Stem Cells (hiPSCs)-derived neuronal cultures to study neural communicational dynamics during early development in SZ. We conducted gene and protein expression profiling, calcium imaging recordings, and applied a mathematical model to quantify the dynamism of functional connectivity (FC) in hiPSCs-derived neuronal networks. Along the neurodifferentiation process, SZ networks displayed altered gene expression of the glutamate receptor-related proteins HOMER1 and GRIN1 compared to healthy control (HC) networks, suggesting a possible tendency to develop hyperexcitability. Resting-state FC in neuronal networks derived from HC and SZ patients emerged as a dynamic phenomenon exhibiting connectivity configurations reoccurring in time (hub states). Compared to HC, SZ networks were less thorough in exploring different FC configurations, changed configurations less often, presented a reduced repertoire of hub states and spent longer uninterrupted time intervals in this less diverse universe of hubs. Our results suggest that alterations in the communicational dynamics of SZ emerging neuronal networks might contribute to the previously described brain FC anomalies in SZ patients, by compromising the ability of their neuronal networks for rapid and efficient reorganization through different activity patterns.https://www.frontiersin.org/articles/10.3389/fcell.2022.935360/fullschizophrenianeural stem cells (NSCs)hiPSCsresting-state functional connectivitycalcium imagingneurodevelopment |
| spellingShingle | Sofía Puvogel Sofía Puvogel Kris Blanchard Kris Blanchard Bárbara S. Casas Robyn L. Miller Robyn L. Miller Delia Garrido-Jara Sebastián Arizabalos Stevens K. Rehen Magdalena Sanhueza Verónica Palma Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients Frontiers in Cell and Developmental Biology schizophrenia neural stem cells (NSCs) hiPSCs resting-state functional connectivity calcium imaging neurodevelopment |
| title | Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients |
| title_full | Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients |
| title_fullStr | Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients |
| title_full_unstemmed | Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients |
| title_short | Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients |
| title_sort | altered resting state functional connectivity in hipscs derived neuronal networks from schizophrenia patients |
| topic | schizophrenia neural stem cells (NSCs) hiPSCs resting-state functional connectivity calcium imaging neurodevelopment |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.935360/full |
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