title: Transplantation of neural stem cells co-transfected with Nurr1 and Brn4 for treatment of Parkinsonian rats.
abstract: Neural stem cells (NSCs) tranplantation has great potential for the treatment of neurodegenerative disease such as Parkinson's disease (PD). However, the usage of NSCs is limited because the differentiation of NSCs into specific dopaminergic neurons has proven difficult. We have recently demonstrated that transgenic expression of Nurr1 could induce the differentiation of NSCs into tyrosine hydroxylase (TH) immunoreactive dopaminergic neurons, and forced co-expression of Nurr1 with Brn4 caused a dramatic increase in morphological and phenotypical maturity of these neurons. In this study, we investigated the effect of transplanted NSCs in PD model rats. The results showed that overexpression of Nurr1 promoted NSCs to differentiate into dopaminergic neurons in vivo, increased the level of dopamine (DA) neurotransmitter in the striatum, resulting in behavioral improvement of PD rats. Importantly, co-expression of Nurr1 and Brn4 in NSCs significantly increased the maturity and viability of dopaminergic neurons, further raised the DA amount in the striatum and reversed the behavioral deficit of the PD rats. Our findings provide a new potential and strategy for the use of NSCs in cell replacement therapy for PD.
authors.affiliation: Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, PR China. tanxuefeng1977@163.com
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Tan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: JianBing
authors.initials: J
authors.lastname: Qin
authors.forename: Meiling
authors.initials: M
authors.lastname: Tian
authors.forename: Huixia
authors.initials: H
authors.lastname: Zhu
authors.forename: Chuanming
authors.initials: C
authors.lastname: Dong
authors.forename: Heyan
authors.initials: H
authors.lastname: Zhao
authors.forename: Guohua
authors.initials: G
authors.lastname: Jin
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001058:Apomorphine; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D050809:POU Domain Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D050809:POU Domain Factors; C484088:Pou3f4 protein, rat; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine