Intrapallidal lipopolysaccharide injection increases iron and ferritin levels in glia of the rat substantia nigra and induces locomotor deficits

J. Zhang, D. M. Stanton, X. V. Nguyen, M. Liu, Z. Zhang, D. Gash, G. Bing

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Increasing evidence suggests that abnormal iron handling may be involved in the pathogenesis of Parkinson's disease. The present study investigates the role of iron and the iron-storage protein ferritin in inflammation-induced degeneration of dopaminergic neurons of the substantia nigra pars compacta. Injection of lipopolysaccharide into the globus pallidus of young and middle-aged rats substantially decreased tyrosine hydroxylase immunostaining in substantia nigra pars compacta four weeks after injection. Loss of tyrosine hydroxylase expression was accompanied by increased iron and ferritin levels in glial cells of the substantia nigra pars reticulata. Despite greater increases in nigral iron levels, ferritin induction was less pronounced in older rats, suggesting the regulation of ferritin was compromised with age. Automated movement tracking analyses showed that young rats recovered from LPS-induced locomotor deficits within four weeks, yet older rats failed to improve on measures of speed and total distance moved. Intrapallidal lipopolysaccharide injection also increased expression of α-synuclein and ubiquitin in tyrosine hydroxylase-positive neurons of the substantia nigra pars compacta. These results suggest that pallidal inflammation significantly increases stress on dopamine-containing neurons in the substantia nigra pars compacta. Alterations in nigral iron levels and protein handing may increase the vulnerability of nigral neurons to degenerative processes.

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalNeuroscience
Volume135
Issue number3
DOIs
StatePublished - 2005

Bibliographical note

Funding Information:
Grant sponsor: National Institutes of Health grant NS39345, NS044157 (G.Y.B.), AG13494 (D.M.G.); grant sponsor: U.S. Army; grant number: DAMD 17–9919497 (G.Y.B). National Natural Science Foundation of China, No. 30430280 (J.Z).

Keywords

  • Alpha-synuclein
  • Globus pallidus
  • Inflammation
  • Microglia
  • Oxidative stress
  • Ubiquitin

ASJC Scopus subject areas

  • General Neuroscience

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