Intrastriatal lipopolysaccharide injection induces parkinsonism in C57/B6 mice.
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.
Hunter
Randy L
RL
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA.
Cheng
Baohua
B
Choi
Dong-Young
DY
Liu
Mei
M
Liu
Shuwei
S
Cass
Wayne A
WA
Bing
Guoying
G
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000172:deficiency; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D004298:Dopamine