Iron accumulation in the striatum predicts aging-related decline in motor function in rhesus monkeys

Wayne A. Cass, Richard Grondin, Anders H. Andersen, Zhiming Zhang, Peter A. Hardy, Lindsay K. Hussey-Andersen, William S. Rayens, Greg A. Gerhardt, Don M. Gash

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Changes in the nigrostriatal system may be involved with the motor abnormalities seen in aging. These perturbations include alterations in dopamine (DA) release, regulation and transport in the striatum and substantia nigra, striatal atrophy and elevated iron levels in the basal ganglia. However, the relative contribution of these changes to the motor deficits seen in aging is unclear. Thus, using the rhesus monkey as a model, the present study was designed to examine several of these key alterations in the basal ganglia in order to help elucidate the mechanisms contributing to age-related motor decline. First, 32 female rhesus monkeys ranging from 4 to 32 years old were evaluated for their motor capabilities using an automated hand-retrieval task. Second, non-invasive MRI methods were used to estimate brain composition and to indirectly measure relative iron content in the striatum and substantia nigra. Third, in vivo microdialysis was used to evaluate basal and stimulus-evoked levels of DA and its metabolites in the striatum and substantia nigra of the same monkeys. Our results demonstrated significant decreases in motor performance, decreases in striatal DA release, and increases in striatal iron levels in rhesus monkeys as they age from young adulthood. A comprehensive statistical analysis relating age, motor performance, DA release, and iron content indicated that the best predictor of decreases in motor ability, above and beyond levels of performance that could be explained by age alone, was iron accumulation in the striatum. This suggests that striatal iron levels may be a biomarker of motor dysfunction in aging; and as such, can be monitored non-invasively by longitudinal brain MRI scans. The results also suggest that treatments aimed at reducing accumulation of excess iron in the striatum during normal aging may have beneficial effects on age-related deterioration of motor performance.

Original languageEnglish
Pages (from-to)258-271
Number of pages14
JournalNeurobiology of Aging
Issue number2
StatePublished - Feb 2007

Bibliographical note

Funding Information:
We wish to thank Robin Avison, Agnes Bognar, George A. Day, Michael Dunlap, Eric Forman, Sheila McLean, Laura E. Peters, Michael P. Smith, John A. Stanford and Ashley Walton for technical assistance. This study was supported in part by United States Public Health Service Grants AG13494, AG17963 and NS39787. None of the authors have a conflict of interest of any type in association with this work.


  • Aging
  • Dopamine
  • Iron levels
  • MRI
  • Microdialysis
  • Motor function

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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