期刊
PARKINSONISM & RELATED DISORDERS
卷 13, 期 2, 页码 77-88出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2006.07.015
关键词
neural stem cell; neurturin; Parkinson's disease; neuroprotection
Genetically engineered neural stem cell (NSC) lines are promising vectors for the treatment of regenerative diseases, especially Parkinson's disease (PD). Neurturin (NTN), a member of the glial cell line-derived neurotrophic factor-family, has been demonstrated to act specifically on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for PD. Here, we have generated a NTN-secreting c17.2 NSC line and investigated the protective effect of NTN-c17.2 on PD rat models. These NTN-releasing NSCs engrafted and integrated in the host striatum with good success, gave rise to neurons, astrocytes and oligodendrocytes, and maintained stable, high-level NTN expression. In addition, inverse transfer of NTN protein into the substantia nigra (SN) was able to protect dopaminergic neurons from 6-OHDA toxicity. Observation of rotational behavior showed that the NTN group performed significantly better than the Mock group, and the protective effect of NTN lasted for at least 4 months. H PLC tests indicated that the contents of neuro transmitters (e.g. dopamine) in the corpus striatum area of the NTN-c17.2 group and the Mock-c17.2 group were significantly higher than in the PBS group, but there was no significant difference between expression in the NTN-cl7.2 and Mock-17.2 groups. Taken together, our results suggest that transplantation of NTN-secreting NSCs exerted protective on PD rat models. (c) 2006 Elsevier Ltd. All rights reserved.
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