Altered glutamate response and calcium dynamics in iPSC-derived striatal neurons from XDP patients.

Altered glutamate response and calcium dynamics in iPSC-derived striatal neurons from XDP patients. Exp Neurol. 2018 Jun 23;: Authors: Capetian P, Stanslowsky N, Bernhardi E, Grütz K, Domingo A, Brüggemann N, Naujock M, Seibler P, Klein C, Wegner F Abstract X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disorder endemic to Panay Island (Philippines). Patients present with generalizing dystonia and parkinsonism. Genetic changes surrounding the TAF1 (TATA-box binding protein associated factor 1) gene have been associated with XDP inducing a degeneration of striatal spiny projection neurons. There is little knowledge about the pathophysiology of this disorder. Our objective was to generate and analyze an in-vitro model of XDP based on striatal neurons differentiated from induced pluripotent stem cells (iPSC). We generated iPSC from patient and healthy control fibroblasts (3 affected, 3 controls), followed by directed differentiation of the cultures towards striatal neurons. Cells underwent characterization of immunophenotype as well as neuronal function, glutamate receptor properties and calcium dynamics by whole-cell patch-clamp recordings and calcium imaging. Furthermore, we evaluated expression levels of AMPA receptor subunits and voltage-gated calcium channels by quantitative real-time PCR. We observed no differences in basic electrophysiological properties. Application of the AMPA antagonist NBQX led to a more pronou...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research