Factors involved in the determination of the neurotransmitter phenotype of developing neurons of the CNS: applications in cell replacement treatment for Parkinson's disease

The developmental stages involved in the conversion of stem cells to fully functional neurons of specific neurotransmitter phenotype are complex and not fully understood. Over the past decade many studies have been published that demonstrate that in vitro manipulation of the epigenetic environment of the stem cells allows experimental control of final neuronal phenotypic choice. This review presents the evidence for the involvement of a number of endogenous neurobiochemicals, which have been reported to potently influence DAergic (and other neurotransmitter) phenotype expression in vitro. They act at different stages on the pathway to neurotransmitter phenotype determination, and in different ways. Many are better known for their involvement in other aspects of development, and in other biochemical roles. Their proper place, and precise roles, in neurotransmitter phenotype determination in vivo will no doubt be determined in the future. Meanwhile, considerable medical benefits are offered from producing large, long-term, viable cryostores of self-regenerating multipotential neural precursor cells (i.e., brain stem cells), which can be used for cell replacement therapies in the treatment of degenerative brain diseases, such as Parkinson's disease.