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

作　　者：Jiao-Tian Xu Yuan Qian Wei Wang Xiao-Xiang Chen Yang Li Yu Li Zhi-Yong Yang Xiao-Bin Song Di Lu Xing-Li Deng 

机构地区：[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

出　　处：《Neural Regeneration Research》2020年第1期112-119,共8页中国神经再生研究（英文版）

基　　金：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)

摘　　要：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 5μL 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 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 × 10~4/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

关 键 词：AMD3100 corpus STRIATUM CXCR4 neural stem cells Parkinson’s disease STROMAL cell-derived factor-1 substantia nigra 

分 类 号：R459.9[医药卫生—治疗学] R741[医药卫生—临床医学]