The first two authors contributed equally to this work.
Intrastriatal lipopolysaccharide injection induces parkinsonism in C57/B6 mice
Article first published online: 17 FEB 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 87, Issue 8, pages 1913–1921, June 2009
How to Cite
Hunter, R. L., Cheng, B., Choi, D.-Y., Liu, M., Liu, S., Cass, W. A. and Bing, G. (2009), Intrastriatal lipopolysaccharide injection induces parkinsonism in C57/B6 mice. J. Neurosci. Res., 87: 1913–1921. doi: 10.1002/jnr.22012
- Issue published online: 13 APR 2009
- Article first published online: 17 FEB 2009
- Manuscript Accepted: 26 NOV 2008
- Manuscript Revised: 20 OCT 2008
- Manuscript Received: 4 AUG 2008
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke. Grant Numbers: AG017963, NS044157
- oxidative stress;
- nitric oxide
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. © 2009 Wiley-Liss, Inc.