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Characterization of the lipopolysaccharide induced model of Parkinson's disease: Role of oxidative stress and neuroinflammation.

Abstract：

INTRODUCTION:Primary pathology underlying Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra (SN). A variety of genetic and environmental factors underlie this loss of dopaminergic neurons. However, recent studies have highlighted the role of elevated oxidative stress and the pro-inflammatory responses contributing to or exacerbating the nigrostriatal degeneration. METHODS:With the establishment of neuroinflammation as an important process involved in the PD pathogenesis, in the present study this pathogenic feature was replicated in animals using lipopolysaccharide (LPS) (5 ug/5 ul PBS) infused stereotaxically into the SN of rats. RESULTS:LPS injected into the SN successfully replicated the pathogenic features of PD in rats as it elicited an inflammatory response via action of microglia. LPS infusion resulted in glial cell activation as depicted from immunohistochemistry (IHC) analysis of GFAP and Iba-1. Also, a significant increase in the mRNA expression of proinflammatory cytokines, i.e. TNF-α and IL-1β, was observed after 7 days of LPS infusion whereas the alterations in the oxidative stress markers, i.e ROS, lipid peroxidation, NO formation, NADPH oxidase activity, glutathione system, SOD and catalase, became highly significant after 14 days of infusion. As a consequence, after 21 days of LPS infusion we observed activation of apoptotic pathway indicated by increased expression of caspases 3 and caspase 9. This was followed by a significant decline in the expression of tyrosine hyroxylase (TH) as revealed by IHC. Further, there was a marked decrease in the level of dopamine and its metabolites enough for the production of behavioral abnormality in rats. CONCLUSION:Hence, the present study provides extensive characterization of LPS induced model of PD. Study also confirms the co-existence and complex interplay between inflammation and oxidative stress contributing equally to the dopaminergic neuronal degeneration process in PD.

journal_name

Neurochem Int

journal_title

Neurochemistry international

authors

Sharma N,Nehru B

doi

10.1016/j.neuint.2015.06.004

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

92-105

eissn

0197-0186

issn

1872-9754

pii

S0197-0186(15)00088-1

journal_volume

87

pub_type

杂志文章

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