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Functional and transcriptional characterization of complex neuronal co-cultures
- Source :
- Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020), Scientific Reports, Scientific reports, vol 10, iss 1
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....c7d8db6a32e53d3d63360194e401cb83