Functional Integration of Grafted Neural Stem Cell-Derived Dopaminergic Neurons Monitored by Optogenetics in an In Vitro Parkinson Model
Jan Tonnesen, Clare L Parish, Andreas T Sorensen, Angelica Andersson, Cecilia Lundberg, Karl Deisseroth, Ernest Arenas, Olle Lindvall, Merab Kokaia
PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2011
Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These propertie..View full abstract
Awarded by European Community
Awarded by Excell
This study is supported by grants from the European Community's Seventh Framework Programme through NeuroStemcell (nr. 22943) and Excell (nr. 214706), The Swedish Research Council, The Royal Physiographic Society, and Lars Hierta's Memorial and Kock Foundations. CLP is supported by a National Health & Medical Research Council Career Development Award Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.