Abstract: Objective To evaluate the therapeutic effect of transplantation of mesencephalic neural stem cells (mNSCs)
genetically modified by glial cell line-derived neurotrophic factor (GDNF) gene in a rat model of Parkinson disease. Methods
mNSCs isolated from the lateral component of the midbrain of fetal rats at gestational age of 14 or 15 days were cultured for 5
days before genetic modification with GFP or GDNF gene. Rat models of Parkinson disease established by stereotactic
injection of 6-hydroxy dopamine in the ventral area of the midbrain and the medial forebrain bundle were randomized into 3
groups to receive PBS injection, GFP gene-modified mNSCs transplantation, or GDNF gene-modified mNSCs transplantation
into the right stratum. The behavioral changes of the rats were evaluated by observing rotations induced by intraperitoneal
injection of apomorphine after the transplantation, and the survival, migration and differentiation of the transplanted cells
were identified by immunohistochemistry. Results Transplantation with GDNF gene-modified mNSCs significantly improved
the behavioral abnormalities of the rat models as compared with PBS injection and GFP gene-modified mNSCs
transplantation. At 56 days after the transplantation, a greater number of the transplanted cells survived in the rat brain and
more differentiated dopaminergic neurons were detected in GDNF gene-modified mNSCs transplantation group than in GFP
gene-modified mNSCs transplantation group. Conclusion GDNF gene-modified mNSCs transplantation can significantly
improve dyskinesia in rat models of Parkinson disease, but the molecular mechanism needs further clarification.