Investigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain

dc.contributor.advisorRaimondo, Joseph
dc.contributor.advisorSteyn, Teresa
dc.contributor.authorKundieko, Sagel
dc.date.accessioned2025-12-10T10:54:15Z
dc.date.available2025-12-10T10:54:15Z
dc.date.issued2025
dc.date.updated2025-12-10T10:52:07Z
dc.description.abstractOrganotypic brain slice cultures (OBSCs) are widely used to study neural circuit function, but their molecular and cellular composition relative to acute brain slices remains poorly characterized. Here, using single-nucleus RNA sequencing, I performed a comprehensive comparison of gene expression between OBSCs and acute brain slices prepared from postnatal day 7 mouse hippocampus. I identified significant differences in cellular composition, with OBSCs showing an overrepresentation of glial cells and a relative underrepresentation of neuronal populations. Notably, oligodendrocytes were almost exclusively found in OBSCs, while dentate progenitor cells were predominantly present in acute slices, reflecting ongoing developmental processes in culture. Differential gene expression analysis revealed over 4200 unique differentially expressed genes across major cell types, with excitatory neurons and astrocytes showing the most substantial transcriptional changes. Gene ontology analysis demonstrated upregulation of pathways involved in neuronal development and cell signalling alongside downregulation of axon guidance pathways in OBSCs. Specific cell-type analysis revealed distinct adaptations, including altered inflammatory responses in microglia and astrocytes as well as modified synaptic signalling in dentate gyrus cells. These findings provide crucial insights into how brain slice cultures adapt to ex vivo conditions and highlight important considerations for their use as experimental models in neuroscience research.
dc.identifier.apacitationKundieko, S. (2025). <i>Investigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain</i>. (). University of Cape Town ,Faculty of Health Sciences ,Department of Human Biology. Retrieved from http://hdl.handle.net/11427/42422en_ZA
dc.identifier.chicagocitationKundieko, Sagel. <i>"Investigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain."</i> ., University of Cape Town ,Faculty of Health Sciences ,Department of Human Biology, 2025. http://hdl.handle.net/11427/42422en_ZA
dc.identifier.citationKundieko, S. 2025. Investigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain. . University of Cape Town ,Faculty of Health Sciences ,Department of Human Biology. http://hdl.handle.net/11427/42422en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Kundieko, Sagel AB - Organotypic brain slice cultures (OBSCs) are widely used to study neural circuit function, but their molecular and cellular composition relative to acute brain slices remains poorly characterized. Here, using single-nucleus RNA sequencing, I performed a comprehensive comparison of gene expression between OBSCs and acute brain slices prepared from postnatal day 7 mouse hippocampus. I identified significant differences in cellular composition, with OBSCs showing an overrepresentation of glial cells and a relative underrepresentation of neuronal populations. Notably, oligodendrocytes were almost exclusively found in OBSCs, while dentate progenitor cells were predominantly present in acute slices, reflecting ongoing developmental processes in culture. Differential gene expression analysis revealed over 4200 unique differentially expressed genes across major cell types, with excitatory neurons and astrocytes showing the most substantial transcriptional changes. Gene ontology analysis demonstrated upregulation of pathways involved in neuronal development and cell signalling alongside downregulation of axon guidance pathways in OBSCs. Specific cell-type analysis revealed distinct adaptations, including altered inflammatory responses in microglia and astrocytes as well as modified synaptic signalling in dentate gyrus cells. These findings provide crucial insights into how brain slice cultures adapt to ex vivo conditions and highlight important considerations for their use as experimental models in neuroscience research. DA - 2025 DB - OpenUCT DP - University of Cape Town KW - Medicine KW - Neuroscience LK - https://open.uct.ac.za PB - University of Cape Town PY - 2025 T1 - Investigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain TI - Investigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain UR - http://hdl.handle.net/11427/42422 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/42422
dc.identifier.vancouvercitationKundieko S. Investigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain. []. University of Cape Town ,Faculty of Health Sciences ,Department of Human Biology, 2025 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/42422en_ZA
dc.language.isoen
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Human Biology
dc.publisher.facultyFaculty of Health Sciences
dc.publisher.institutionUniversity of Cape Town
dc.subjectMedicine
dc.subjectNeuroscience
dc.titleInvestigating gene expression differences in acute and organotypic mouse hippocampal brain slices as models for studying the brain
dc.typeThesis / Dissertation
dc.type.qualificationlevelMasters
dc.type.qualificationlevelMSc
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