Nurr1Cd11bcre conditional knockout mice display inflammatory injury to nigrostriatal dopaminergic neurons

Jie Dong, Xinyao Liu, Yuanyuan Wang, Huaibin Cai, Weidong Le

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 deleted Nurr1 in the microglia of Nurr1Cd11bcre conditional knockout (cKO) mice. The Nurr1Cd11bcre 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) to Nurr1Cd11bcre mice. As expected, LPS treatment exacerbated the motor phenotypes and inflammatory reactions in Nurr1Cd11bcre cKO mice. More importantly, LPS administration caused DAergic neuron loss and α-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.

Original languageEnglish (US)
Pages (from-to)2057-2069
Number of pages13
JournalGLIA
Volume68
Issue number10
DOIs
StatePublished - Oct 1 2020

Keywords

  • Nurr1
  • Parkinson's disease
  • microglia
  • neurodegeneration
  • neuroinflammation

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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