Effects of resveratrol on the transplantation of neural stem cell-derived dopaminergic neurons in a rat model of Parkinson's disease

ABSTRACT

BACKGROUND:

Dopaminergic neurons differentiated from neural stem cells have been successfully used in the treatment of Parkinson's disease rats; however, the survival rate of transplanted cells has been low. Most cells die of apoptosis as a result of the formation of oxygen free radical and lipid peroxidation.

To observe resveratrol (Res) effects on survival of transplanted cells, transplanted efficacy and dopaminergic differentiation from neural stem cells in a rat model of Parkinson's disease.DESIGN, TIME AND

Randomized controlled animal experiments were performed at the Animal Experiment Center,Sun Yat-sen University from October 2007 to June 2008.MATERIALS Thirty-two adult, healthy, male Sprague Dawley rats were equally and randomly assigned to model control, dopaminergic neuron, Res and combination groups. Four healthy Sprague Dawley rat embryos at gastational days 14-15 were selected and fetal rats were used for isolation and culture of neural stem cells. Res (Jingmal Biotech, Shenzhen, China) was used for this study.

Neural stem cells derived from the mesencephalon of embryonic rats were isolated and cultured in vitro, and passaged in serum-free culture medium containing epidermal growth factor and basic fibroblast growth factor, and then differentiated into dopaminergic neurons in differentia.ion medium. Parkinson's disease rat models were established by the injection of 6-hydroxydopamine in each group. Rats in the dopaminergic neuron group was injected with 3 pL cell suspension (1×10 cells/μL) containing dopaminergic neurons in the corpus striatum. Rats in the Res group received 3 μL of Ras (40 mg/L).Rats in the combination group were subjected to 3 μL of Res (40 mg/L) + 3 μL cell suspension (1×105 calls/μL) containing dopaminergic neurons. Rats in the model control group received 3 ×L of DMEM/F12 culture medium.MAIN OUTCOME

The percentage of tyrosine hydroxylase-positive neurons in differentiated cells. The alteration of rotational asymmetry and the survival of tyrosine hydroxylase-positive neurons in graft areas of Parkinson's disease rats after transplantation.

Flow cytometry demonstrated that survival rate of tyrosine hydroxytase-positive neurons was (17.8 ±4.2)% at 6 days following differentiation. Compared to the model control group, the rotational asymmetry was significantly improved at 10 days (P < 0.01), was significantly decreased at 20 days following transplantation in the combination group (P < 0.01). At 10-60 days following transplantation, the number of rotational asymmetry was significantly lower in the combination group than in the dopaminergic neuron group (P < 0.01). Tyrosine hydroxylase-positive neurons were not determined in the Res and model control groups. The number of tyrosine hydroxylase-positive neurons was significantly more in the combination group than in the dopaminergic neuron group (P < 0.01).

Res can increase survival rate of transplanted cells in the corpus striatum, and improve rotational asymmetry in rat models of Parkinson's disease following transplantation of dopaminergic neurons differentiated from neural stem cells.Ke CL, Chen BL, Yu ZH, Huang ZS.Effects of resveratrol on the transplantation of neural stem call-derived dopaminergic neurons in a rat model of Parkinson's disease.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu. 2009;13(27) 5281-5285.[http//www.crter.on http//en.zglckf.com]