Investigating hiPSC Derived Neurons and iDISCO+ as Tools For Neurite Morphology Quantification in Neurodevelopmental Disorders
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2018-02-01
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en
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Neurodevelopmental Disorders (NDDs) have a severe impact on affected individuals. Social and cognitive problems emerge, often accompanied by intellectual disability and/or autism spectrum disorder. Since NDDs have diverse causes and comorbid phenotypes, it is essential to assess them on multiple levels.
Recent developments in cellular neurobiology make modeling the patient phenotype in a dish possible, with induced Neurons (iNeurons). However, iNeurons cannot provide the 3D structural level of a full brain. The iDISCO+ method for 3D immunolabeling of whole organisms could surpass the need for sectioning methods, which usually destroy neuronal connections. In this study, we assess the suitability of both methods for quantifying dendrite morphology. For the iNeurons, three different models of NDDs were cultured, imaged and reconstructed, namely Koolen- de Vries Syndrome (KdV), Kleefstra Syndrome (KS) and Mitochondrial encephalomyopathy and lactic acidosis Syndrome (MELAS). Contrary to previous animal model quantification results we hardly detected any differences in the three NDD models between patient and control lines. KdV and KS neurons dendrite morphology is not affected. Furthermore, we show that iNeurons are a well suited model for dendrite morphology assessment. Qualitative analysis of iDISCO+ results demonstrates that it is a useful tool to study dendrite morphology in a 3D context.
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Faculteit der Sociale Wetenschappen