Open AccessNurr1 promotes neurogenesis of dopaminergic neuron and represses inflammatory factors in the transwell coculture system of neural stem cells and microglia
Author(s) -
Chen XiaoXiang,
Qian Yuan,
Wang XiangPeng,
Tang ZhiWei,
Xu JiaoTian,
Lin Hai,
Yang ZhiYong,
Song XiaoBin,
Lu Di,
Guo JiaZhi,
Bian LiGong,
Li Yu,
Zhou Lei,
Deng XingLi
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12825
Subject(s) - neuroinflammation , microglia , neurogenesis , dopaminergic , neural stem cell , neuroscience , embryonic stem cell , biology , transplantation , substantia nigra , microbiology and biotechnology , dopamine , stem cell , immunology , inflammation , medicine , biochemistry , gene
Summary Introduction Neural stem cells ( NSC s) are the most promising cells for cell replacement therapy for Parkinson's disease ( PD ). However, a majority of the transplanted NSC s differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA ( mDA ) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor‐related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life. Aim This study investigated the effect of Nurr1 on neuroinflammation and differentiation of NSC s cocultured with primary microglia in the transwell coculture system. Results The results showed that Nurr1 exerted anti‐inflammatory effects and promoted the differentiation of NSC s into dopaminergic neurons. Conclusions The results suggested that Nurr1 protects dopaminergic neurons from neuroinflammation insults by limiting the production of neurotoxic mediators by microglia and maintain the survival of transplanted NSC s. These phenomena provided a new theoretical and experimental foundation for the transplantation of Nurr1‐overexpressed NSC s as a potential treatment of PD .