Nurr1(Cd11bcre)Conditional Knockout Mice Display Inflammatory Injury To Nigrostriatal Dopaminergic Neurons

Nuclear receptor-related 1 protein (NURR1) is essential for the development and maintenance of midbrain dopaminergic (DAergic) neurons. NURR1 also protects DAergic neurons against neuroinflammation. However, it remains to be determined to what extent does NURR1 exerts its protective function through acting autonomously in the microglia. Using Cre/lox gene targeting system, we deletedNurr1in the microglia ofNurr1(Cd11bcre)conditional knockout (cKO) mice. TheNurr1(Cd11bcre)cKO mice displayed age-dependent motor abnormalities and increased microglial activation, but with no obvious DAergic neurodegeneration. To boost the inflammatory injury, we systemically administered endotoxin lipopolysaccharide (LPS) toNurr1(Cd11bcre)mice. As expected, LPS treatment exacerbated the motor phenotypes and inflammatory reactions inNurr1(Cd11bcre)cKO mice. More importantly, LPS administration caused DAergic neuron loss and alpha-synuclein aggregation, two pathological hallmarks of Parkinson's disease (PD). Therefore, our findings provide in vivo evidence supporting a critical protective role of NURR1 in the microglia against inflammation-induced degeneration of DAergic neurons in PD.