Intrastriatal lipopolysaccharide injection induces Parkinsonism in C57/B6 mice

Randy L. Hunter, Baohua Cheng, Dong Young Choi, Mei Liu, Shuwei Liu, Wayne A. Cass, Guoying Bing

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

A role for inflammation has been hypothesized in the etiology and progression of Parkinson's disease (PD). In this study, we generated, characterized, and validated the first progressive PD-related mouse model (C57/B6) with intrastriatal injection of lipopolysaccharide (LPS). We showed progressive and specific dopaminergic neurodegeneration in the substantia nigra, which is accompanied by striatal dopamine depletion and progressive behavioral impairment, which was alleviated by the use of the PD drug L-Dopa. We focused on the role of nitric oxide (NO) in inflammation-promoted cell death and suggest that the expression of the inducible NO synthase plays a role in the progressive loss of dopaminergic neurons but not the initial loss induced by LPS. With this model, future research can be performed in gene knockout mice to study other potential mechanisms of inflammation-induced neurodegeneration. In addition, this model can be used to screen therapeutics for PD at a more clinically relevant time (i.e., after LPS injection but before manifestation of PD-related behavioral impairment), because most PD drugs are screened in animal models in which inhibitors are given predisease induction. Thus, this novel PD-related model should be further characterized and strongly considered as a tool for future drug studies.

Original languageEnglish
Pages (from-to)1913-1921
Number of pages9
JournalJournal of Neuroscience Research
Volume87
Issue number8
DOIs
StatePublished - 2009

Keywords

  • Inflammation
  • Neurodegeneration
  • Nitric oxide
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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