Stem cell in disease and treatment

Increase of measurable dopamine level in striatum but not in CSF after transplantation of dopaminergic neuronal precursors into Parkinson’ disease animal model

*Hsiao-Nan Hao1, 3, Jean Peduzzi2, Peter Hao1, Deqi Xiang3, Hua Tong4

Depts of Orthopaedic Surgery1 & Cell Biology/Anatomy2, Wayne State University, Detroit, MI. USA 48201; Xiamen Neocell Bio-Technology Developmental Inc.3 ; PLA458 Hospital, Guangzhou, China4

 Transplantation of dopaminergic neuronal precursors into the brain basal ganglia is a potential cell replacement therapy (CRT) for the patients with Parkinson disease (PD). The expectation result of the cell transplantation is to elevate the level of dopamine (DOP) in the specific areas of central nervous system (CNS) in order to alleviate the clinical motor symptoms of PD. However, over producing of DOP may induce psychological manifestations. There are many reported clinical results indicate that increasing the level of DOP in CSF highly associates with psychological symptoms. Therefore, monitoring the level of DOP in CSF becomes a prioritized test to Parkinsonism treated with CRT.  In this study, the DOP levels in both brain tissue and CSF were measured from both intracranial inoculation groups with (5,000 cells/0.1ml PBS) and without (0.1ml PBS) dopaminergic neuronal precursor cell transplantation. The results of this study show that the levels of DOP in CSF were no significant elevation from both of the animals received with or without cell transplantations. In contrast, the levels of DOP in the basal ganglia tissues (including caudate, putamen, globus pallidus, substantia nigra and subthalamic nucleus) are elevated from the group received dopaminergic neuronal precursors transplantation by biochemistry and regional immunohistochemistry stains. We also measured the dopamine levels from both groups of animals received non-dopaminergic neuronal cell (5,000 cells/0.1ml PBS) intracranial inoculation and dopaminergic neuronal precursor cells (5,000 cells/0.1ml PBS). The results of biochemical analysis clearly show the elevated DOP level in the basal ganglia tissue extracted from the animal received dopaminergic neuronal precursor cell transplantation. The immunohistochemistry studies of basal ganglia regional specific slice preparations strongly support biochemical analysis. The experimental data suggest that the transplanted dopaminergic neuronal precursor cells can produce DOP, and possibly limit in a “synapse-communication” physiological working condition. The results also indicate that the non-dopamine produced neuronal cells are unable to stimulate the PD animals to produce DO in vivo. Due to lack of the detail morphological evidence of transplanted cells, a further study of cell-cell synapse communication is deserved. 

Posted by: Hsiao-Nan Hao, Asistant professor , Wayne State University, United States (15-Apr-2012)