Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson's disease

M. P. Smith, W. A. Cass

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69 Scopus citations

Abstract

Although the etiology of Parkinson's disease (PD) is unknown, a common element of most theories is the involvement of oxidative stress, either as a cause or effect of the disease. There have been relatively few studies that have characterized oxidative stress in animal models of PD. In the present study a 6-hydroxydopamine (6-OHDA) rodent model of PD was used to investigate the in vivo production of oxidative stress after administration of the neurotoxin. 6-OHDA was injected into the striatum of young adult rats and the production of protein carbonyls and 4-hydroxynonenal (HNE) was measured at 1, 3, 7, and 14 days after administration. A significant increase in both markers was found in the striatum 1 day after neurotoxin administration, and this increase declined to basal levels by day 7. There was no significant increase found in the substantia nigra at any of the time points investigated. This same lesion paradigm produced dopamine depletions of 90-95% in the striatum and 63-80% in the substantia nigra by 14-28 days post-6-OHDA. Protein carbonyl and HNE levels were also measured in middle-aged and aged animals 1 day after striatal 6-OHDA. Both protein carbonyl and HNE levels were increased in the striatum of middle-aged and aged animals treated with 6-OHDA, but the increases were not as great as those observed in the young adult animals. Similar to the young animals, there were no increases in either marker in the substantia nigra of the middle-aged and aged animals. There was a trend for an age-dependent increase in basal amounts of oxidative stress markers when comparing the non-lesioned side of the brains of the three age groups. These results support that an early event in the course of dopamine depletion following intrastriatal 6-OHDA administration is the generation of oxidative stress.

Original languageEnglish
Pages (from-to)1057-1066
Number of pages10
JournalNeuroscience
Volume144
Issue number3
DOIs
StatePublished - Feb 9 2007

Bibliographical note

Funding Information:
We thank Laura Peters, Brian Thompson, Dr. H. Fei Poon, and Dr. Ed Hall for technical assistance and for discussions concerning the experiments. This study was supported in part by United States Public Health Service Grants AG17963 and AG00242.

Keywords

  • 4-hydroxynonenal
  • aging
  • protein carbonyls
  • reactive oxygen species
  • striatum
  • substantia nigra

ASJC Scopus subject areas

  • General Neuroscience

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