Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway

Randy Hunter, Uttam Ojha, Sunil Bhurtel, Guoying Bing, Dong Young Choi

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Accumulating evidence suggests that chronic inflammation plays a role in the progressive dopaminergic neurodegeneration that occurs in Parkinson's disease. It has been hypothesized that inflammation mediates neuronal damage via exacerbation of a vicious cycle of oxidative stress and mitochondrial dysfunction. The bacterial endotoxin, lipopolysaccharide (LPS), induces microglial activation and inflammation driven dopaminergic neurodegeneration. In order to test the hypothesis that LPS-induced inflammatory response might damage mitochondrial structure and function leading to nigral dopaminergic neuron loss, we injected LPS or saline into the striatum of rats. Here, we found that intrastriatal LPS induced deficit in mitochondrial respiration, damage to mitochondrial cristae, mitochondrial oxidation and nitration. Finally, we found significant loss of dopaminergic neurons in the substantia nigra one week after LPS injection. This study indicates that LPS-induced dopaminergic neurodegeneration might be exerted by mitochondrial injury.

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalNeuroscience Research
Volume114
DOIs
StatePublished - Jan 1 2017

Keywords

  • Lipopolysaccharide
  • Mitochondria
  • Neuroinflammation
  • Oxidative stress
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience (all)

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