Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease

Yu Bing Dai, Xin Jie Tan, Wan Fu Wu, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Parkinson disease (PD) is a progressive neurodegenerative disease whose progression may be slowed, but at present there is no pharmacological intervention that would stop or reverse the disease. Liver X receptor β (LXRβ) is a member of the nuclear receptor super gene family expressed in the central nervous system, where it is important for cortical layering during development and survival of dopaminergic neurons throughout life. In the present study we have used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate the possible use of LXRβ as a target for prevention or treatment of PD. The dopaminergic neurons of the substantia nigra of LXRβ-/- mice were much more severely affected by MPTP than were those of their WT littermates. In addition, the number of activated microglia and GFAPpositive astrocytes was higher in the substantia nigra of LXRβ-/-mice than in WT littermates. Administration of the LXR agonist GW3965 to MPTP-treated WT mice protected against loss of dopaminergic neurons and of dopaminergic fibers projecting to the striatum, and resulted in fewer activated microglia and astroglia. Surprisingly, LXRβ was not expressed in the neurons of the substantia nigra but in the microglia and astroglia. We conclude that LXR agonists may have beneficial effects in treatment of PD by modulating the cytotoxic functions of microglia.

Original languageEnglish (US)
Pages (from-to)13112-13117
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number32
DOIs
StatePublished - Aug 7 2012

Keywords

  • Midbrain
  • Neurodegeneration
  • Neuroinflammation

ASJC Scopus subject areas

  • General

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