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Author (up) Kuijlaars, J.; Oyelami, T.; Diels, A.; Rohrbacher, J.; Versweyveld, S.; Meneghello, G.; Tuefferd, M.; Verstraelen, P.; Detrez, J.R.; Verschuuren, M.; De Vos, W.H.; Meert, T.; Peeters, P.J.; Cik, M.; Nuydens, R.; Brone, B.; Verheyen, A. url  doi
  Title Sustained synchronized neuronal network activity in a human astrocyte co-culture system Type Journal Article
  Year 2016 Publication Scientific Reports Abbreviated Journal Sci Rep  
  Volume 6 Issue Pages 36529  
  Abstract Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells. However, the differentiation process and growth conditions of hiPSC-derived neurons are non-trivial. In order to study neuronal network formation and (mal)function in a fully humanized system, we have established an in vitro co-culture model of hiPSC-derived cortical neurons and human primary astrocytes that recapitulates neuronal network synchronization and connectivity within three to four weeks after final plating. Live cell calcium imaging, electrophysiology and high content image analyses revealed an increased maturation of network functionality and synchronicity over time for co-cultures compared to neuronal monocultures. The cells express GABAergic and glutamatergic markers and respond to inhibitors of both neurotransmitter pathways in a functional assay. The combination of this co-culture model with quantitative imaging of network morphofunction is amenable to high throughput screening for lead discovery and drug optimization for neurological diseases.  
  Address Janssen Research &Development, a division of Janssen Pharmaceutica N.V, Beerse, B-2340, Belgium  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2045-2322 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27819315; PMCID:PMC5098163 Approved no  
  Call Number refbase @ user @ Serial 16646  
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