Iron accumulation in the striatum predicts aging-related decline in motor function in rhesus monkeys
Abstract
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 expla…
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Two-step processing of human frataxin gives rise to an intermediate (aa 42 to 210) and mature (aa 56 to 210) frataxin.
“Similarly, the two-step processing of human frataxin was shown to give rise to an intermediate (aa 42 to 210) and mature (aa 56 to 210) frataxin (43)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [43]
Both yeast and human frataxin are processed to a mature form in two sequential cleavage steps with a mitochondrial processing peptidase (MPP).
“It was shown that both yeast and human frataxin are processed to a mature form in two sequential cleavage steps with a mitochondrial processing peptidase (MPP) (28, 43, 167)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [43]
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- Authors
- Cass, W. A., Grondin, R., Andersen, A. H., Zhang, Z., Hardy, P. A., Hussey-Andersen, L. K., Rayens, W. S., Gerhardt, G. A., & Gash, D. M.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Cass, Wayne A.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 28
- Issue
- 2
- Pages
- 258-271
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1970032686
- Cited by
- 67
- References
- 67
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 4 · 2022: 2 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 7
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- National Institute on Aging (P01AG013494, R01AG017963, AG 13494, AG17963)
- National Institute of Neurological Disorders and Stroke (P50NS039787, NS 39787)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- age-related motor decline, nigrostriatal pathway, dopamine release, substantia nigra, basal ganglia, rhesus monkeys, dopamine metabolites, striatal atrophy
- MeSH terms
- Aging, Animals, Brain Mapping, Corpus Striatum, Disease Models, Animal, Dopamine, Female, Iron, Macaca mulatta, Magnetic Resonance Imaging, Motor Skills, Movement, Movement Disorders, Prognosis, Task Performance and Analysis, Tissue Distribution
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