Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (1): 112-119.doi: 10.4103/1673-5374.264470

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Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson’s disease

Jiao-Tian Xu1, Yuan Qian2, Wei Wang1, 3, Xiao-Xiang Chen1, Yang Li1, Yu Li1, Zhi-Yong Yang1, Xiao-Bin Song1, Di Lu4, Xing-Li Deng1   

  1. 1 Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
    2 Diagnosis Prenatal Unit, Department of Obstetrics, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
    3 The People’s Hospital of Chuxiong Yi Autonomous Prefecture, Chuxiong, Yunnan Province, China
    4 Rehabilitation Engineering Research Laboratory, Biomedicine Engineering Research Center, Kunming Medical University, Kunming, Yunnan Province, China
  • Online:2020-01-15 Published:2020-05-20
  • Contact: Xing-Li Deng, MD,dxlkmmu@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81241126 (to XLD) and 81360197 (to XLD);
    a grant from the Department of Science and Technology of Kunming Medical University in China, No. 2013C227 (to XLD); the Joint Special Fund for the Department of Science and Technology of Kunming Medical University in China, No. 2014FB041 (to XBS).

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Abstract:

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease, but its specific mechanism of action is still unclear. Stromal cell-derived factor-1 and its receptor, chemokine receptor 4 (CXCR4), are important regulators of cell migration. We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease. A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway, and then treated with 5 μL of neural stem cell suspension (1.5 × 104/L) in the right substantia nigra. Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation. Parkinson-like behavior in rats was detected using apomorphine-induced rotation. Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase, CXCR4, and stromal cell-derived factor-1 in the brain. Using quantitative real-time polymerase chain reaction, the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured. In addition, western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4. Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation, increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra, and enhanced the immunoreactivity of tyrosine hydroxylase, CXCR4, and stromal cell-derived factor-1 in the brain. Injection of AMD3100 inhibited the aforementioned effects. These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease. This study was approved by the Animal Care and Use Committee of Kunming Medical University, China (approval No. SYXKK2015-0002) on April 1, 2014.

Key words: AMD3100, corpus striatum, CXCR4, neural stem cells, Parkinson’s disease, stromal cell-derived factor-1, substantia nigra