Depletion of microglia augments the dopaminergic neurotoxicity of MPTP

Xiaoxia Yang, Honglei Ren, Kristofer Wood, Minshu Li, Shenfeng Qiu, Fu Dong Shi, Cungen Ma, Qiang Liu

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The activation ofmicroglia and the various substances they produce have been linked to the pathologic development of Parkinson's disease (PD), but the precise role ofmicroglia inPDremains tobe defined.The survival of microglia depends on colony-stimulating factor 1 receptor (CSF1R) signaling, and CSF1R inhibition results in rapid elimination of microglia in the central nervous system. Using a mouse PD model induced by 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment, we showed that the depletion of microglia via the CSF1R inhibitor PLX3397 exacerbated the impairment of locomotor activities and the loss of dopaminergic neurons. Further, depletion of microglia augmented the production of inflammatorymediators and infiltration of leukocytes in the brain after MPTP exposure. Microglia depletion-induced aggravation of MPTP neurotoxicity was also seen in lymphocyte-deficientmice. In addition, the depletion ofmicroglia did not affect the production of brain-derived neurotrophic factor, but it dramatically augmented the production of inflammatory mediators by astrocytes after MPTP treatment. Our findings suggest microglia play a protective role against MPTP-induced neuroinflammation and dopaminergicneurotoxicity.

Original languageEnglish (US)
Pages (from-to)3336-3345
Number of pages10
JournalFASEB Journal
Volume32
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

  • MPTP
  • Neuroprotection
  • Parkinson's disease

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Yang, X., Ren, H., Wood, K., Li, M., Qiu, S., Shi, F. D., Ma, C., & Liu, Q. (2018). Depletion of microglia augments the dopaminergic neurotoxicity of MPTP. FASEB Journal, 32(6), 3336-3345. https://doi.org/10.1096/fj.201700833RR