Reference:
MJD350
Abstract:
Cellular and molecular studies of the human brain are mostly performed on postmortem tissue or animal models. Recently however, induced pluripotent cell (iPSCs) technology has become a valuable tool that enables studies on live human iPSC-derived neurons, thus providing an alternative approach with clear advantages over animal models or postmortem tissue for research on neuropsychiatric disorders. Disruption of regulation and/or function of activity-dependent gene expression in neurons has been found to constitute a significant factor among the causes of neuropsychiatric disorders. Yet, neuronal activity-regulated transcription has been most studied in rodent models. This project proposes the use of human iPSC-derived neurons for systematic characterization of neuronal activity-dependent regulation of gene transcription in human cells and assessment whether this model system is suitable for detecting defects in regulation of neuronal gene expression in genetic diseases. The aims of the project are to differentiate human iPSCs into glutamatergic neurons, to analyze the electrophysiological properties of the differentiated cells and to thoroughly characterize calcium signaling and activation of activity-regulated molecular pathways in these neurons. Additionally, an objective is to identify the activity-regulated genes in human iPSC-derived neurons. Furthermore, to test the feasibility of iPSC-derived neuron model system for detecting aberrations in gene regulation in neuropsychiatric disorders, regulation of activity-dependent transcription and genes induced by neuronal activity in iPSC-derived neurons generated from the autism spectrum disorder Rett syndrome patientsﾒ fibroblasts will be analyzed. The results of the project would provide substantial information on neuronal activity-dependent gene expression regulation in human neurons and facilitate research on neurodevelopmental and neuropsychiatric disorders with complex genetic origin.
PROJECT DETAILS
beginning: 2012.
end: 2015.
Country of research: Estonia
Counry of funding source: Estonia
Funding organization: Estonian Science Foundation
Financing: NATIONAL FUNDINGS – 0 €