Transplantation of Nurr1 Gene-modified Embryo Midbrain Neural Stem Cells for Treatment in Parkinson’ s Disease

Yi-sheng QIAO; Xiao-xiang CHEN; Jiao-tian XU; Wei WANG; Chao ZHANG; Xiao-bin SONG; Zhi-yong YANG; Xing-li DENG

doi:10.12259/j.issn.2095-610X.S20210801

Volume 42 Issue 8

Aug. 2021

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Article Navigation > Journal of Kunming Medical University > 2021 > 42(8): 1-6

Yi-sheng QIAO, Xiao-xiang CHEN, Jiao-tian XU, Wei WANG, Chao ZHANG, Xiao-bin SONG, Zhi-yong YANG, Xing-li DENG. Transplantation of Nurr1 Gene-modified Embryo Midbrain Neural Stem Cells for Treatment in Parkinson’ s Disease[J]. Journal of Kunming Medical University, 2021, 42(8): 1-6. doi: 10.12259/j.issn.2095-610X.S20210801

Citation:

Yi-sheng QIAO, Xiao-xiang CHEN, Jiao-tian XU, Wei WANG, Chao ZHANG, Xiao-bin SONG, Zhi-yong YANG, Xing-li DENG. Transplantation of Nurr1 Gene-modified Embryo Midbrain Neural Stem Cells for Treatment in Parkinson’ s Disease[J]. Journal of Kunming Medical University, 2021, 42(8): 1-6. doi: 10.12259/j.issn.2095-610X.S20210801

Citation:

Yi-sheng QIAO, Xiao-xiang CHEN, Jiao-tian XU, Wei WANG, Chao ZHANG, Xiao-bin SONG, Zhi-yong YANG, Xing-li DENG. Transplantation of Nurr1 Gene-modified Embryo Midbrain Neural Stem Cells for Treatment in Parkinson’ s Disease[J]. Journal of Kunming Medical University, 2021, 42(8): 1-6. doi: 10.12259/j.issn.2095-610X.S20210801

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Transplantation of Nurr1 Gene-modified Embryo Midbrain Neural Stem Cells for Treatment in Parkinson’ s Disease

doi: 10.12259/j.issn.2095-610X.S20210801

1.
Dept. of Neurosurgery，The 1st Affiliated Hospital, Kunming Medical University， Kunming Yunnan 650032
2.
Neurology Center of Northeast Yunnan Regional Central Hospital，Zhaotong Yunnan 547000，China

Received Date: 2021-06-13
Available Online: 2021-08-04
Publish Date: 2021-08-04

Abstract

Abstract

Objective To investigate the therapeutic effect of transplanted Nurr1 gene-modified embryo midbrain neural stem cells in Parkinson’ s rats. Methods 1. Establishment of Parkinson’ s disease animal model in SD rats. 2. Primary culture of embryo midbrain neural stem cells （NCSs） and Nurr1 gene-modified neural stem cells. 3. Grouping: sham operation group （sham group）, Transplanted neural stem cell group （NCS group）, transplanted Nurr1 gene-modified neural stem cells group （NNCS group）. 4. At 3 weeks, 6 weeks, 9 weeks, and 12 weeks after the transplantation, the behavioral tests of rats in each group were performed to observe the improvement of symptoms in each group. 5. After 12 weeks of transplantation, the expression of Nurr1, TH protein and Nurr1 fluorescence were detected in each group. Results 1. Primary cultured neural stem cells, and successfully overexpressed Nurr1 in neural stem cells. 2. Overexpression of Nurr1 could promote the transformation of neural stem cells into dopaminergic neurons （P < 0.05）, which was confirmed by immunofluorescence and Western Blot. 3. Transplantation of NNCS can effectively improve the symptoms of rats with Parkinson’ s （P < 0.05）. 4. After transplantation, Nurr1 can promote the transformation of neural stem cells into dopaminergic neurons, greatly improve the survival of transplanted neural stem cells and achieve better therapeutic effect. Conclusion Nurr1 can promote the transformation of neural stem cells into dopaminergic neurons. Transplantation of overexpression of Nurr1 neural stem cells can effectively treat Parkinson’ s rats.
- Nurr1,
- Embryonic stem cells,
- Parkinson disease

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References(18)

References

[1]	Balestrino R,Schapira A H V. Parkinson disease[J]. Eur J Neurol,2020,27(1):27-42.
[2]	陈彪. 左旋多巴在帕金森病治疗中的地位及进展[J]. 中国临床神经科学,2017,25(5):546-550. doi: 10.3969/j.issn.1008-0678.2017.05.012
[3]	Zhu B,Caldwell M,Song B. Development of stem cell-based therapies for Parkinson’ s disease[J]. Int J Neurosci,2016,126(11):955-962.
[4]	Zhang Q,Chen W,Tan S,et al. Stem cells for modeling and therapy of parkinson’ s disease[J]. Hum Gene Ther,2017,28(1):85-98. doi: 10.1089/hum.2016.116
[5]	刘罡,吴毅,贾杰,等. 神经干细胞体外分化抗原表达的研究[J]. 中国运动医学杂志,2009,28(1):55-59.
[6]	Li K, Li J, Zheng J, Qin S. Reactive astrocytes in neurodegenerative diseases[J]. Aging Dis. 2019; 10(3): 664-675.
[7]	Barker R A,Drouin Ooellet J,Parmar M. Cell-based therapies for Parkinson disease-past insights and future potential[J]. Nat Rev Neurol,2015,11(9):492-503. doi: 10.1038/nrneurol.2015.123
[8]	徐蛟天,陈孝祥,王威,等. Nurr1对小胶质细胞联合神经干细胞共培养促进神经干细胞向多巴胺神经元分化作用研究[J]. 国际神经病学神经外科学杂志,2018,45(01):52-57.
[9]	Liu W,Gao Y,Chang N. Nurr1 overexpression exerts neuroprotective and anti-inflammatory roles via down-regulating CCL2 expression in both in vivo and in vitro Parkinson’ s disease models[J]. Biochem Biophys Res Commun,2017,482(4):1312-1319. doi: 10.1016/j.bbrc.2016.12.034
[10]	Kadkhodaei B,Ito T,Joodmardi E,et al. Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons[J]. J Neurosci,2009,29(50):15923-15932. doi: 10.1523/JNEUROSCI.3910-09.2009
[11]	Radad K,Moldzio R,AL-Shraim M,et al. Recent advances on the role of neurogenesis in the adult brain:Therapeutic potential in parkinson’ s and Alzheimer’ s diseases[J]. CNS Neurol Disord Drug Targets,2017,16(7):740-748.
[12]	O’ sullivan S S,Johnson M,Williams D R,et al. The effect of drug treatment on neurogenesis in parkinson's disease[J]. Mov Disord,2011,26(1):45-50. doi: 10.1002/mds.23340
[13]	Madhavan L,Daley B F,Paumier K L,et al. Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson’ s disease[J]. J Comp Neurol,2009,515(1):102-115. doi: 10.1002/cne.22033
[14]	Dong J,Liu X,Wang Y,et al. Nurr1(Cd11bcre) conditional knockout mice display inflammatory injury to nigrostriatal dopaminergic neurons[J]. Glia,2020,68(10):2057-2069. doi: 10.1002/glia.23826
[15]	Wang X,Zhuang W,Fu W,et al. The lentiviral-mediated Nurr1 genetic engineering mesenchymal stem cells protect dopaminergic neurons in a rat model of Parkinson’ s disease[J]. Am J Transl Res,2018,10(6):1583-1599.
[16]	Smith G A,Rocha E M,Rooney T,et al. A Nurr1 agonist causes neuroprotection in a Parkinson’ s disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly (I:C)[J]. PLoS One,2015,10(3):e0121072. doi: 10.1371/journal.pone.0121072
[17]	Ahmed A,Isaksen T J,Yamashita T. Protocol for mouse adult neural stem cell isolation and culture[J]. STAR Protoc,2021,2(2):100522. doi: 10.1016/j.xpro.2021.100522
[18]	Raina A,Mahajani S,Bahr M,et al. Neuronal trans-differentiation by traNCSription factors ascl1 and Nurr1:Induction of a dopaminergic neurotransmitter phenotype in cortical GABAergic neurons[J]. Mol Neurobiol,2020,57(1):249-260. doi: 10.1007/s12035-019-01701-x

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