The effect of rho kinase inhibition on morphological and electrophysiological maturity in iPSC-derived neurons
| Autor: | Nadine Michel, Mark P. Beenhakker, Lise J Harbom, Taylor Rudisill, Michael J. McConnell, Karen A Litwa |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Histology Neurite Pyridines Induced Pluripotent Stem Cells Article Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurites Premovement neuronal activity Humans Induced pluripotent stem cell Rho-associated protein kinase Cell Shape Protein Kinase Inhibitors Membrane potential Neurons rho-Associated Kinases Chemistry Neurogenesis Cell Biology Amides Cell biology Electrophysiological Phenomena Y-27632 Electrophysiology 030104 developmental biology 030217 neurology & neurosurgery |
| Zdroj: | Cell and tissue research. 375(3) |
| ISSN: | 1432-0878 |
| Popis: | Induced pluripotent stem cell (iPSC)-derived neurons permit the study of neurogenesis and neurological disease in a human setting. However, the electrophysiological properties of iPSC-derived neurons are consistent with those observed in immature cortical neurons, including a high membrane resistance, depolarized resting membrane potential, and immature firing properties, limiting their use in modelling neuronal activity in adult cells. Based on the proven association between inhibiting rho kinase (ROCK) and increased neurite complexity, we sought to determine if short-term ROCK inhibition during the first 1–2 weeks of differentiation would increase morphological complexity and electrophysiological maturity after several weeks of differentiation. While inhibiting ROCK resulted in increased neurite formation after 24 hours, this effect did not persist at 3 and 6 weeks of age. Additionally, there was no effect of ROCK inhibition on electrophysiological properties at 2–3, 6, or 12 weeks of age, despite an increase in evoked and spontaneous firing and a more hyperpolarized resting membrane potential over time. These results indicates that while there is a clear effect of time on electrophysiological maturity, ROCK inhibition did not accelerate maturity. |
| Databáze: | OpenAIRE |
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