scholarly journals Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells

2013 ◽  
Vol 110 (7) ◽  
pp. E602-E610 ◽  
Author(s):  
E. R. Andersson ◽  
C. Salto ◽  
J. C. Villaescusa ◽  
L. Cajanek ◽  
S. Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dopaminergic Neurons ◽  
Midbrain Dopaminergic Neurons

scholarly journals BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo and in Human Induced Pluripotent and Neural Stem Cells

2018 ◽  
Vol 38 (7) ◽  
pp. 1662-1676 ◽  
Author(s):  
Vukasin M. Jovanovic ◽  
Ahmad Salti ◽  
Hadas Tilleman ◽  
Ksenija Zega ◽  
Marin M. Jukic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dopaminergic Neurons ◽  
Smad Pathway ◽  
Midbrain Dopaminergic Neurons ◽  
Induced Pluripotent

scholarly journals Human Mesenchymal Stromal Cells Unveil an Unexpected Differentiation Potential toward the Dopaminergic Neuronal Lineage

2020 ◽  
Vol 21 (18) ◽  
pp. 6589
Author(s):  
Giulia Gaggi ◽  
Andrea Di Credico ◽  
Pascal Izzicupo ◽  
Francesco Alviano ◽  
Michele Di Mauro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Dopaminergic Neurons ◽  
High Efficiency ◽  
Ethical Issues ◽  
Differentiation Potential ◽  
Homogeneous Population ◽  
Human Mesenchymal Stromal Cells ◽  
Midbrain Dopaminergic Neurons

Degeneration of dopaminergic neurons represents the cause of many neurodegenerative diseases, with increasing incidence worldwide. The replacement of dead cells with new healthy ones may represent an appealing therapeutic approach to these pathologies, but currently, only pluripotent stem cells can generate dopaminergic neurons with high efficiency. However, with the use of these cells arises safety and/or ethical issues. Human mesenchymal stromal cells (hFM-MSCs) are perinatal stem cells that can be easily isolated from the amniochorionic membrane after delivery. Generally considered multipotent, their real differentiative potential is not completely elucidated. The aim of this study was to analyze their stemness characteristics and to evaluate whether they may overcome their mesenchymal fate, generating dopaminergic neurons. We demonstrated that hFM-MSCs expressed embryonal genes OCT4, NANOG, SOX2, KLF4, OVOL1, and ESG1, suggesting they have some features of pluripotency. Moreover, hFM-MSCs that underwent a dopaminergic differentiation protocol gradually increased the transcription of dopaminergic markers LMX1b, NURR1, PITX3, and DAT. We finally obtained a homogeneous population of cells resembling the morphology of primary midbrain dopaminergic neurons that expressed the functional dopaminergic markers TH, DAT, and Nurr1. In conclusion, our results suggested that hFM-MSCs retain the expression of pluripotency genes and are able to differentiate not only into mesodermal cells, but also into neuroectodermal dopaminergic neuron-like cells.

Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo

1994 ◽  
Vol 182 (1) ◽  
pp. 107-111 ◽  
Author(s):  
Barry J. Hoffer ◽  
Alex Hoffman ◽  
Kate Bowenkamp ◽  
Peter Huettl ◽  
John Hudson ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Midbrain Dopaminergic Neurons

Subcortical excitatory inputs to nigral dopaminergic and non-dopaminergic neurons: A light and Electron Microscopic study

1993 ◽  
Vol 51 ◽  
pp. 94-95
Author(s):  
Meri Damlama ◽  
James M. Tepper
Keyword(s):  
Dopaminergic Neurons ◽  
Motor Disorders ◽  
Survival Times ◽  
Normal Functioning ◽  
Electron Microscopic ◽  
Midbrain Dopaminergic Neurons ◽  
Anterograde Tracers ◽  
Afferent Inputs

Midbrain dopaminergic neurons are involved in the symptomotology of motor disorders such as Parkinsonism as well as psychiatric disorders such as schizophrenia. The normal functioning of substantia nigra (SN) dopaminergic neurons is greatly influenced by their afferent inputs as evidenced by significant differences in the physiological characteristics of in vivo vs. in vitro preparations. Although the sources and neurotransmitters of many afferents to the SN are known, because dopaminergic and non-dopaminergic dendrites co-mingle in pars reticulata, the precise postsynaptic targets, particularly those of the presumed excitatory inputs, remain to be determined. In the present study inputs from the subthalamic (STN) and the pedunculopontine (PPN) nuclei (both presumed excitatory) to the SN were investigated by combined anterograde tracing and tyrosine hydroxylase (TH) immunocytochemistry at the light and electron microscopic levels.The anterograde tracers biocytin or PHA-L were iontophoretically injected into either the STN or the PPN. Following appropriate survival times the animals were perfused transcardially with a mixture of 4% paraformaldehyde and 0.2% glutaraldehyde.

scholarly journals High-frequency, short-latency disinhibition bursting of midbrain dopaminergic neurons

2011 ◽  
Vol 105 (5) ◽  
pp. 2501-2511 ◽  
Author(s):  
Collin J. Lobb ◽  
Charles J. Wilson ◽  
Carlos A. Paladini
Keyword(s):  
High Frequency ◽  
Dopaminergic Neurons ◽  
Time Course ◽  
Firing Frequency ◽  
Short Latency ◽  
Inhibitory Input ◽  
In Vivo Experiments ◽  
Midbrain Dopaminergic Neurons ◽  
Inhibitory Conductance

During reinforcement and sequence learning, dopaminergic neurons fire bursts of action potentials. Dopaminergic neurons in vivo receive strong background excitatory and inhibitory inputs, suggesting that one mechanism by which bursts may be produced is disinhibition. Unfortunately, these inputs are lost during slice preparation and are not precisely controlled during in vivo experiments. In the present study we show that dopaminergic neurons can be shifted into a balanced state in which constant synaptic N-methyl-d-aspartate (NMDA) and GABAA conductances are mimicked either pharmacologically or using dynamic clamp. From this state, a disinhibition burst can be evoked by removing the background inhibitory conductance. We demonstrate three functional characteristics of network-based disinhibition that promote high-frequency, short-latency bursting in dopaminergic neurons. First, we found that increasing the total background NMDA and GABAA synaptic conductances increased the intraburst firing frequency and reduced its latency. Second, we found that the disinhibition burst is sensitive to the proportion of background inhibitory input that is removed. In particular, we found that high-frequency, short-latency bursts were enhanced by increasing the degree of disinhibition. Third, the time course over which inhibition is removed had a large effect on the burst, namely, that synchronous removal of weak inhibitory inputs produces bursts of high intraburst frequency and shorter latency. Our results suggest that fast, more precisely timed bursts can be evoked by complete and synchronous disinhibition of dopaminergic neurons in a high-conductance state.

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