Functional and transcriptional characterization of complex neuronal co-cultures
| Autor: | Nicholas R. Hum, Doris Lam, Bryan Petkus, Heather A. Enright, Kristen S. Kulp, Joanne Osburn, Elizabeth K. Wheeler, David A. Soscia, Sandra K. G. Peters, Ana Paula Sales, Jose Cadena, Nicholas O. Fischer, Gabriela G. Loots, Aimy Sebastian |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cells
1.1 Normal biological development and functioning Neurogenesis Cell Synaptophysin lcsh:Medicine Neurodegenerative Article Synapse Transcriptome Underpinning research Lab-On-A-Chip Devices medicine Premovement neuronal activity Animals Gene Regulatory Networks lcsh:Science Cells Cultured Cultured Multidisciplinary biology Sequence Analysis RNA Gene Expression Profiling lcsh:R Neurosciences Bicuculline GABA receptor antagonist Cellular neuroscience Coculture Techniques Brain Disorders Cell biology Rats Oligodendroglia medicine.anatomical_structure Cell culture Astrocytes Neurological biology.protein Neuronal physiology RNA lcsh:Q Single-Cell Analysis Sequence Analysis Biotechnology medicine.drug |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) Scientific Reports Scientific reports, vol 10, iss 1 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-67691-2 |
| Popis: | Brain-on-a-chip systems are designed to simulate brain activity using traditional in vitro cell culture on an engineered platform. It is a noninvasive tool to screen new drugs, evaluate toxicants, and elucidate disease mechanisms. However, successful recapitulation of brain function on these systems is dependent on the complexity of the cell culture. In this study, we increased cellular complexity of traditional (simple) neuronal cultures by co-culturing with astrocytes and oligodendrocyte precursor cells (complex culture). We evaluated and compared neuronal activity (e.g., network formation and maturation), cellular composition in long-term culture, and the transcriptome of the two cultures. Compared to simple cultures, neurons from complex co-cultures exhibited earlier synapse and network development and maturation, which was supported by localized synaptophysin expression, up-regulation of genes involved in mature neuronal processes, and synchronized neural network activity. Also, mature oligodendrocytes and reactive astrocytes were only detected in complex cultures upon transcriptomic analysis of age-matched cultures. Functionally, the GABA antagonist bicuculline had a greater influence on bursting activity in complex versus simple cultures. Collectively, the cellular complexity of brain-on-a-chip systems intrinsically develops cell type-specific phenotypes relevant to the brain while accelerating the maturation of neuronal networks, important features underdeveloped in traditional cultures. |
| Databáze: | OpenAIRE |
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