TY  - JOUR
A1  - Stengel, Felix
A1  - Vulinovic, Franca
A1  - Meier, Britta
A1  - Grütz, Karen
A1  - Klein, Christine
A1  - Capetian, Philipp
T1  - Impaired differentiation of human induced neural stem cells by TOR1A overexpression
JF  - Molecular Biology Reports
N2  - DYT-TOR1A is the most common inherited dystonia caused by a three nucleotide (GAG) deletion (dE) in the TOR1A gene. Death early after birth and cortical anomalies of the full knockout in rodents underscore its developmental importance. We therefore explored the timed effects of TOR1A-wt and TOR1A-dE during differentiation in a human neural in vitro model. We used lentiviral tet-ON expression of TOR1A-wt and -dE in induced neural stem cells derived from healthy donors. Overexpression was induced during proliferation of neural precursors, during differentiation and after differentiation into mature neurons. Overexpression of both wildtype and mutated protein had no effect on the viability and cell number of neural precursors as well as mature neurons when initiated before or after differentiation. However, if induced during differentiation, overexpression of TOR1A-wt and -dE led to a pronounced reduction of mature neurons in a dose dependent manner. Our data underscores the importance of physiological expression levels of TOR1A as crucial for proper neuronal differentiation. We did not find evidence for a specific impact of the mutated TOR1A on neuronal maturation.
KW  - dystonia
KW  - DYT1
KW  - torsinA
KW  - TOR1A
KW  - neuronal stem cells
KW  - neuronal differentiation
KW  - inducible expression
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241177
UR  - https://doi.org/10.1007/s11033-020-05390-x
VL  - 47
ER  - 
TY  - JOUR
A1  - Del Vecchio, Jasmin
A1  - Hanafi, Ibrahem
A1  - Pozzi, Nicoló Gabriele
A1  - Capetian, Philipp
A1  - Isaias, Ioannis U.
A1  - Haufe, Stefan
A1  - Palmisano, Chiara
T1  - Pallidal recordings in chronically implanted dystonic patients: mitigation of tremor-related artifacts
JF  - Bioengineering
N2  - Low-frequency oscillatory patterns of pallidal local field potentials (LFPs) have been proposed as a physiomarker for dystonia and hold the promise for personalized adaptive deep brain stimulation. Head tremor, a low-frequency involuntary rhythmic movement typical of cervical dystonia, may cause movement artifacts in LFP signals, compromising the reliability of low-frequency oscillations as biomarkers for adaptive neurostimulation. We investigated chronic pallidal LFPs with the Percept\(^{TM}\) PC (Medtronic PLC) device in eight subjects with dystonia (five with head tremors). We applied a multiple regression approach to pallidal LFPs in patients with head tremors using kinematic information measured with an inertial measurement unit (IMU) and an electromyographic signal (EMG). With IMU regression, we found tremor contamination in all subjects, whereas EMG regression identified it in only three out of five. IMU regression was also superior to EMG regression in removing tremor-related artifacts and resulted in a significant power reduction, especially in the theta-alpha band. Pallido-muscular coherence was affected by a head tremor and disappeared after IMU regression. Our results show that the Percept PC can record low-frequency oscillations but also reveal spectral contamination due to movement artifacts. IMU regression can identify such artifact contamination and be a suitable tool for its removal.
KW  - dystonia
KW  - tremor
KW  - local field potentials
KW  - globus pallidus
KW  - deep brain stimulation
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313498
SN  - 2306-5354
VL  - 10
IS  - 4
ER  -