Dopaminergic differentiation factors

Muscle-derived differentiation factor (MDF) induces tyrosine hydroxylase expression in a variety of central nervous system neurons, including those of striatum, cerebellum, and cortex. Normally, i.e., without MDF, these neurons do not express this enzyme of catecholamine synthesis. Further in vitro studies revealed that MDF enhances TH-mRNA 40-fold in fetal mesencephalic neurons. In vivo studies, employing infusion of partially isolated MDF, reported this molecule to enhance tyrosine hydroxylase activity in dopamine-depleted striata of 6-OHDA-lesioned animals. Furthermore, an increase of striatal dopamine concentrations and a partial compensation of rotational asymmetry were observed. In contrast, dopaminergic parameters were not affected by administration of MDF in control animals, suggesting that adult dopaminergic neurons may regain sensitivity toward differentiation factors after lesion. 

Jin, B.K. and lacovitti, L. (1996) Dopamine differentiation factors increase striatal dopaminergic function in 1-methyl-4phenyl-l,2,3,6tetrahydropyridine (MPTP) - lesioned mice. J. Neurosci. Res. 43 331-334. 

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)...

Tatard VM, Sindji L, Branton JG, et al. Pharmacologically active microcarriers releasing glial cell line—derived neurotrophic factor survival and differentiation of embryonic dopaminergic neurons after grafting in hemiparkinsonian rats. Biomaterials 2007 28 1978-1988. 

D.P., Nikolics, K. and Hefti, F. (1991) Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. Proc. Natl. Acad. Sci. USA 88 961-965. 

Rolletschek A, Chang H, Guan K, et al. (2001). Differentiation of embryonic stem cell-derived dopaminergic neurons is enhanced by survival-promoting factors. Mech. Dev. 105 93-104. 

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