Nurr1 promotes neurogenesis of dopaminergic neuron and represses inflammatory factors in the transwell coculture system of neural stem cells and microglia

• Published in: CNS neuroscience & therapeutics Vol. 24; no. 9; pp. 790 - 800
• Main Authors: Chen, Xiao‐Xiang, Qian, Yuan, Wang, Xiang‐Peng, Tang, Zhi‐Wei, Xu, Jiao‐Tian, Lin, Hai, Yang, Zhi‐Yong, Song, Xiao‐Bin, Lu, Di, Guo, Jia‐Zhi, Bian, Li‐Gong, Li, Yu, Zhou, Lei, Deng, Xing‐Li
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2018; John Wiley and Sons Inc
• Subjects: Animals; Animals, Newborn; Cell Differentiation - physiology; Cells, Cultured; coculture; Coculture Techniques; Degeneration; Dopamine receptors; Dopaminergic Neurons - metabolism; Embryos; Glial cells; HEK293 Cells; Humans; Inflammation; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; inflammatory; Mesencephalon; Microglia; Microglia - metabolism; Movement disorders; Neural stem cells; Neural Stem Cells - metabolism; Neurodegenerative diseases; Neurogenesis; Neurogenesis - physiology; Neurons; Neurotoxicity; Nuclear Receptor Subfamily 4, Group A, Member 2 - biosynthesis; Nuclear receptors; Nurr1; Nurr1 protein; Original; Parkinson's disease; Phenotypes; Rats; Rats, Sprague-Dawley; Stem cells; Therapeutic applications; Transplantation; Nurr1; coculture; neural stem cells; microglia; inflammatory
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.12825

Summary Introduction Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs 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 NSCs cocultured with primary microglia in the transwell coculture system. Results The results showed that Nurr1 exerted anti‐inflammatory effects and promoted the differentiation of NSCs 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 NSCs. These phenomena provided a new theoretical and experimental foundation for the transplantation of Nurr1‐overexpressed NSCs as a potential treatment of PD.