Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks
Summary: Brain organoids derived from human pluripotent stem cells are a promising tool for studying human neurodevelopment and related disorders. Here, we generated long-term cultures of cortical brain organoid slices (cBOS) grown at the air-liquid interphase from regionalized cortical organoids. W...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224006369 |
| _version_ | 1797258695434829824 |
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| author | Laura Petersilie Sonja Heiduschka Joel S.E. Nelson Louis A. Neu Stephanie Le Ruchika Anand Karl W. Kafitz Alessandro Prigione Christine R. Rose |
| author_facet | Laura Petersilie Sonja Heiduschka Joel S.E. Nelson Louis A. Neu Stephanie Le Ruchika Anand Karl W. Kafitz Alessandro Prigione Christine R. Rose |
| author_sort | Laura Petersilie |
| collection | DOAJ |
| description | Summary: Brain organoids derived from human pluripotent stem cells are a promising tool for studying human neurodevelopment and related disorders. Here, we generated long-term cultures of cortical brain organoid slices (cBOS) grown at the air-liquid interphase from regionalized cortical organoids. We show that cBOS host mature neurons and astrocytes organized in complex architecture. Whole-cell patch-clamp demonstrated subthreshold synaptic inputs and action potential firing of neurons. Spontaneous intracellular calcium signals turned into synchronous large-scale oscillations upon combined disinhibition of NMDA receptors and blocking of GABAA receptors. Brief metabolic inhibition to mimic transient energy restriction in the ischemic brain induced reversible intracellular calcium loading of cBOS. Moreover, metabolic inhibition induced a reversible decline in neuronal ATP as revealed by ATeam1.03YEMK. Overall, cBOS provide a powerful platform to assess morphological and functional aspects of human neural cells in intact minimal networks and to address the pathways that drive cellular damage during brain ischemia. |
| first_indexed | 2024-04-24T22:57:37Z |
| format | Article |
| id | doaj.art-f83e373fe09e4483942951f1ce28e66a |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T22:57:37Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f83e373fe09e4483942951f1ce28e66a2024-03-18T04:34:14ZengElsevieriScience2589-00422024-04-01274109415Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networksLaura Petersilie0Sonja Heiduschka1Joel S.E. Nelson2Louis A. Neu3Stephanie Le4Ruchika Anand5Karl W. Kafitz6Alessandro Prigione7Christine R. Rose8Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, GermanyDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital and Heinrich Heine University Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, GermanyDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital and Heinrich Heine University Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Duesseldorf, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, GermanyDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital and Heinrich Heine University Duesseldorf, 40225 Duesseldorf, Germany; Corresponding authorInstitute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, Germany; Corresponding authorSummary: Brain organoids derived from human pluripotent stem cells are a promising tool for studying human neurodevelopment and related disorders. Here, we generated long-term cultures of cortical brain organoid slices (cBOS) grown at the air-liquid interphase from regionalized cortical organoids. We show that cBOS host mature neurons and astrocytes organized in complex architecture. Whole-cell patch-clamp demonstrated subthreshold synaptic inputs and action potential firing of neurons. Spontaneous intracellular calcium signals turned into synchronous large-scale oscillations upon combined disinhibition of NMDA receptors and blocking of GABAA receptors. Brief metabolic inhibition to mimic transient energy restriction in the ischemic brain induced reversible intracellular calcium loading of cBOS. Moreover, metabolic inhibition induced a reversible decline in neuronal ATP as revealed by ATeam1.03YEMK. Overall, cBOS provide a powerful platform to assess morphological and functional aspects of human neural cells in intact minimal networks and to address the pathways that drive cellular damage during brain ischemia.http://www.sciencedirect.com/science/article/pii/S2589004224006369NeuroscienceCellular neuroscienceStem cells research |
| spellingShingle | Laura Petersilie Sonja Heiduschka Joel S.E. Nelson Louis A. Neu Stephanie Le Ruchika Anand Karl W. Kafitz Alessandro Prigione Christine R. Rose Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks iScience Neuroscience Cellular neuroscience Stem cells research |
| title | Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks |
| title_full | Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks |
| title_fullStr | Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks |
| title_full_unstemmed | Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks |
| title_short | Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks |
| title_sort | cortical brain organoid slices cbos for the study of human neural cells in minimal networks |
| topic | Neuroscience Cellular neuroscience Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224006369 |
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