Current Aging Science

Prof. Debomoy K. Lahiri
Department of Psychiatry Indiana University School of Medicine
Indianapolis, IN
USA

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Inflammation and Age-Related Iron Accumulation in F344 Rats

Author(s): Randy L. Hunter, Mei Liu, Dong Young Choi, Wayne A. Cass, Guoying Bing.

Abstract:

Evidence suggests chronic inflammation and iron accumulation may play a role in the pathogenesis of Parkinsons disease (PD) as inflammation and iron levels increase with age and appear in the disease pathology. It is hypothesized that an aggravated inflammatory response and iron accumulation, as a function of age, increase oxidative stress and participate in the pathogenesis of PD. Intracranial injection of the bacterial endotoxin, lipopolysaccharide (LPS), has been shown to induce microglia activation, oxidative stress, mitochondrial impairment, iron accumulation, and dopaminergic neurodegeneration within the substantia nigra. We tested the hypothesis that injection of LPS into the striatum would increase iron accumulation in the substantia nigra of aged rats compared to young ones. Our results showed that four weeks post injection, LPS significantly increased microglia activation, lipid peroxidation, ferritin expression, and total nigral iron content in aged rats. In addition, LPS significantly altered the turnover ratio of homovanillic acid to dopamine. Thus, an age-related increase in iron as well as susceptibility to inflammation may play an important role in PD-related neurodegeneration, as free radicals produced from the inflammatory response can become more toxic through increased ferrous iron catalyzed Fenton Chemistry. This may enhance oxidative stress, exacerbate microglia activation, and drive the progression of PD.

Keywords: Parkinson's disease, LPS, microglia, oxidative stress

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Article Details

VOLUME: 1
ISSUE: 2
Year: 2008
Page: [112 - 121]
Pages: 10
DOI: 10.2174/1874609810801020112
Price: $58