Dopaminergic neurons, differentiation from

Figure 14.19 Simplified schematic overview of the directed differentiation of human embryonic stem cells to form differentiated dopamine like neurons. The full pathway details are available in Yan, Y., Yang, D., Zarnowska, E.D., Du, Z., Werbel, B., Valliere, C., etai 2005. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23, 781-790. FGF fibroblast growth factor SHH sonic hedgehog (a regulatory protein)...

Human-derived cellular models hold promises in PD modeling and drug discovery. Development of culture systems based on dopaminergic neurons derived from patients with the familial or sporadic PD may enable the discovery of new neuroprotective candidates to work synergistically with currently approved pharmacological therapies. Initial work in this field includes the differentiation of human embryonic stem cells (hESCs) into neurons of dopaminergic identity [96]. 

The segregation or abundance of Di and D2 DA receptor subtypes on the direct and indirect striatal projection neurons indicates that the dopaminergic input arising from midbrain cell groups affects differentially the function of the striatal neuronal populations. At the striatal level, DA appears to facilitate the striatonigral neurons of the direct pathway through Di receptors, and to inhibit the striatopallidal neurons of the indirect pathway through D2 receptors. 

Guloglu, M.O., Larsen, A., Brundin, P Adipocytes derived from PA6 cells leUably promote the differentiation of dopaminergic neurons from humem embryonic stem ceUs. J. Neurosci. Res. 92, 564-573 (2014)... 

Another system in the brain, the basal ganglia, has also been subject of particularly intense research. BDNF, NT-3 and NT-4/5, but not NGF, have shown clear effects on differentiation of both dopaminergic and GABAergic neurons of the ventral mesencephalon. Moreover, NT-3 has also been shown to promote the survival of both populations of neurons (Hyman et al., 1994, Studer et al., 1995). In addition, the presence of trkB and trkC receptors in the striatum, together with the existence of receptor-mediated retrograde transport of BDNF and NT-3 from the striatum to the substantia nigra in adult rat brain (Wiegand et al.,... 

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