Functional and transcriptional characterization of complex neuronal co-cultures
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.
- Authors:
-
[1];
[1];
[1];
[1];
[1]
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1651194
- Report Number(s):
- LLNL-JRNL-767110
Journal ID: ISSN 2045-2322; 957584
- Grant/Contract Number:
- AC52-07NA27344; 17-SI-002; 20-ERD-009
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Cellular neuroscience; neuronal physiology
Citation Formats
Enright, Heather A., Lam, Doris, Sebastian, Aimy, Sales, Ana Paula, Cadena, Jose, Hum, Nicholas R., Osburn, Joanne J., Peters, Sandra G., Petkus, Bryan, Soscia, David A., Kulp, Kristen S., Loots, Gabriela G., Wheeler, Elizabeth K., and Fischer, Nicholas O. Functional and transcriptional characterization of complex neuronal co-cultures. United States: N. p., 2020.
Web. doi:10.1038/s41598-020-67691-2.
Enright, Heather A., Lam, Doris, Sebastian, Aimy, Sales, Ana Paula, Cadena, Jose, Hum, Nicholas R., Osburn, Joanne J., Peters, Sandra G., Petkus, Bryan, Soscia, David A., Kulp, Kristen S., Loots, Gabriela G., Wheeler, Elizabeth K., & Fischer, Nicholas O. Functional and transcriptional characterization of complex neuronal co-cultures. United States. https://doi.org/10.1038/s41598-020-67691-2
Enright, Heather A., Lam, Doris, Sebastian, Aimy, Sales, Ana Paula, Cadena, Jose, Hum, Nicholas R., Osburn, Joanne J., Peters, Sandra G., Petkus, Bryan, Soscia, David A., Kulp, Kristen S., Loots, Gabriela G., Wheeler, Elizabeth K., and Fischer, Nicholas O. Fri .
"Functional and transcriptional characterization of complex neuronal co-cultures". United States. https://doi.org/10.1038/s41598-020-67691-2. https://www.osti.gov/servlets/purl/1651194.
@article{osti_1651194,
title = {Functional and transcriptional characterization of complex neuronal co-cultures},
author = {Enright, Heather A. and Lam, Doris and Sebastian, Aimy and Sales, Ana Paula and Cadena, Jose and Hum, Nicholas R. and Osburn, Joanne J. and Peters, Sandra G. and Petkus, Bryan and Soscia, David A. and Kulp, Kristen S. and Loots, Gabriela G. and Wheeler, Elizabeth K. and Fischer, Nicholas O.},
abstractNote = {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.},
doi = {10.1038/s41598-020-67691-2},
journal = {Scientific Reports},
number = 1,
volume = 10,
place = {United States},
year = {Fri Jul 03 00:00:00 EDT 2020},
month = {Fri Jul 03 00:00:00 EDT 2020}
}
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