TY  - JOUR
A1  - Weider, Matthias
A1  - Wegener, Amélie
A1  - Schmitt, Christian
A1  - Küspert, Melanie
A1  - Hillgärtner, Simone
A1  - Bösl, Michael R.
A1  - Hermans-Borgmeyer, Irm
A1  - Nait-Oumesmar, Brahim
A1  - Wegner, Michael
T1  - Elevated in vivo levels of a single transcription factor directly convert satellite glia into oligodendrocyte-like cells
JF  - PLoS Genetics
N2  - Oligodendrocytes are the myelinating glia of the central nervous system and ensure rapid saltatory conduction. Shortage or loss of these cells leads to severe malfunctions as observed in human leukodystrophies and multiple sclerosis, and their replenishment by reprogramming or cell conversion strategies is an important research aim. Using a transgenic approach we increased levels of the transcription factor Sox10 throughout the mouse embryo and thereby prompted Fabp7-positive glial cells in dorsal root ganglia of the peripheral nervous system to convert into cells with oligodendrocyte characteristics including myelin gene expression. These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage. Instead, Sox10 directly induced key elements of the regulatory network of differentiating oligodendrocytes, including Olig2, Olig1, Nkx2.2 and Myrf. An upstream enhancer mediated the direct induction of the Olig2 gene. Unlike Sox10, Olig2 was not capable of generating oligodendrocyte-like cells in dorsal root ganglia. Our findings provide proof-of-concept that Sox10 can convert conducive cells into oligodendrocyte-like cells in vivo and delineates options for future therapeutic strategies.
KW  - peripheral nervous system
KW  - Hirschsprung disease
KW  - spinal-cord
KW  - boundary cap
KW  - differentiation
KW  - stem cells
KW  - factor Sox10
KW  - mouse model
KW  - expression
KW  - Olig2
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144123
VL  - 11
IS  - 2
ER  - 
TY  - JOUR
A1  - Isaias, Ioannis U.
A1  - Volkmann, Jens
A1  - Marzegan, Alberto
A1  - Marotta, Giorgio
A1  - Cavallari, Paolo
A1  - Pezzoli, Gianni
T1  - The Influence of Dopaminergic Striatal Innervation on Upper Limb Locomotor Synergies
JF  - PLoS One
N2  - To determine the role of striatal dopaminergic innervation on upper limb synergies during walking, we measured arm kinematics in 13 subjects with Parkinson disease. Patients were recruited according to several inclusion criteria to represent the best possible in vivo model of dopaminergic denervation. Of relevance, we included only subjects with normal spatio-temporal parameters of the stride and gait speed to avoid an impairment of upper limbs locomotor synergies as a consequence of gait impairment per se. Dopaminergic innervation of the striatum was measured by FP-CIT and SPECT. All patients showed a reduction of gait-associated arms movement. No linear correlation was found between arm ROM reduction and contralateral dopaminergic putaminal innervation loss. Still, a partition analysis revealed a 80% chance of reduced arm ROM when putaminal dopamine content loss was >47%. A significant correlation was described between the asymmetry indices of the swinging of the two arms and dopaminergic striatal innervation. When arm ROM was reduced, we found a positive correlation between upper-lower limb phase shift modulation ( at different gait velocities) and striatal dopaminergic innervation. These findings are preliminary evidence that dopaminergic striatal tone plays a modulatory role in upper-limb locomotor synergies and upper-lower limb coupling while walking at different velocities.
KW  - pet
KW  - Parkinsons disease
KW  - basal ganglia
KW  - spinal-cord
KW  - walking
KW  - gait
KW  - arm
KW  - coordination
KW  - movements
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133976
VL  - 7
IS  - 12
ER  -