Research article

Dopaminergic regeneration by neurturin-overexpressing c17.2 neural stem cells in a rat model of Parkinson's disease

Wei-Guo Liu^{* 1} , Xi-Jing Wang^{* 1} , Guo-Qiang Lu¹ , Biao Li¹ , Gang Wang¹ and Sheng-Di Chen^1,2

¹Department of Neurology & Neuroscience Institute, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

²Lab of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Science & Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

author email corresponding author email* Contributed equally

Molecular Neurodegeneration 2007, 2:19doi:10.1186/1750-1326-2-19

Published:	1 October 2007

Abstract

Background

Genetically engineered neural stem cell (NSC) lines are promising vectors for the treatment of neurodegenerative diseases, particularly Parkinson's disease (PD). Neurturin (NTN), a member of the glial cell line-derived neurotrophic factor (GDNF) family, has been demonstrated to act specifically on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for PD. In our previous work, we demonstrated that NTN-overexpressing c17.2 NSCs exerted dopaminergic neuroprotection in a rat model of PD. In this study, we transplanted NTN-c17.2 into the striatum of the 6-hydroxydopamine (6-OHDA) PD model to further determine the regenerative effect of NTN-c17.2 on the rat models of PD.

Results

After intrastriatal grafting, NTN-c17.2 cells differentiated and gradually downregulated nestin expression, while the grafts stably overexpressed NTN. Further, an observation of rotational behavior and the contents of neurotransmitters tested by high-performance liquid chromatography showed that the regenerative effect of the NTN-c17.2 group was significantly better than that of the Mock-c17.2 group, and the regenerative effect of the Mock-c17.2 group was better than that of the PBS group. Further research through reverse-transcriptase polymerase chain reaction assays and in vivo histology revealed that the regenerative effect of Mock-c17.2 and NTN-c17.2 cell grafts may be attributed to the ability of NSCs to produce neurotrophic factors and differentiate into tyrosine hydroxylase-positive cells.

Conclusion

The transplantation of NTN-c17.2 can exert neuroregenerative effects in the rat model of PD, and the delivery of NTN by NSCs may constitute a very useful strategy in the treatment of PD.