The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid
Abstract
The mechanisms of delayed onset and cell death in Huntington's disease (HD) are unknown. One possibility is that a genetic defect in energy metabolism may result in slow excitotoxic neuronal death. Therefore, we examined the effects of age on striatal lesions produced by local administration of the mitochondrial toxin 3-nitropropionic acid in rats. In vivo chemical shift magnetic resonance imaging showed marked increases in striatal lactate concentrations that significantly correlated with increasing age. Histologic and neurochemical studies showed a striking age dependence of the lesions, with 4- and 12-month-old animals being much more susceptible than 1-month-old animals. Continuous systemic administration of low doses of 3-nitropropionic acid for 1 month resulted in striatal lesions showing growth-related changes in dendrites of striatal spiny neurons using the Golgi technique. These results show that a known mitochondrial toxin can produce selective axon-sparing striatal lesions showing both the age dependence and striatal spiny neuron dendritic changes that characterize HD.
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“This specific down-regulation of mitochondrial processes in aged striatum could help to explain previous observations demonstrating selective vulnerability to mitochondrial toxins and stresses in the striatum of old animals (Brouillet et al., 1993; Patki et al., 2009).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Brouillet et al., 1993
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Cites
Beal, M. F. (1992) · Annals of Neurology · doi:10.1002/ana.410310202 · Cited by 962
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Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing
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3-Nitropropionic Acid - Exogenous Animal Neurotoxin and Possible Human Striatal Toxin
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Research works printed but not linked: 5
- Beal M. F., 1992, Local and systemic administration of 3‐nitropropionic acid results in excitotoxic striatal lesions, Soc. Neurosci. Abstr., 18, 84
- Koroshetz W. J., 1992, Localized proton‐NMR spectroscopy in patients with Huntington's disease (HD) demonstrates abnormal lactate levels in occipital cortex: evidence for compromised metabolism in HD, Neurology, 42, 319
- Langston J. W., 1989, Aging, Vol. 36: Parkinsonism and Aging, 145
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Cited by
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Oxidative Stress, Glutamate, and Neurodegenerative Disorders
Coyle, J. T., & Puttfarcken, P. (1993) · Science · doi:10.1126/science.7901908 · Cited by 3,762
Aging, energy, and oxidative stress in neurodegenerative diseases
Beal, M. F. (1995) · Annals of Neurology · doi:10.1002/ana.410380304 · Cited by 1,434
Blum, D. L., Torch, S., Lambeng, N., Nissou, M.-F., Benabid, A., Sadoul, R., & Verna, J. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(01)00003-x · Cited by 1,269
Beal, M. F., Brouillet, E., Jenkins, B. G., Ferrante, R. J., Kowall, N. W., Miller, J., Storey, E., Srivastava, R., Rosen, B. R., & Hyman, B. T. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-10-04181.1993 · Cited by 1,026
Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain
Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., & Beal, M. F. (1993) · Annals of Neurology · doi:10.1002/ana.410340416 · Cited by 757
Metadata
- Authors
- Brouillet, E., Jenkins, B. G., Hyman, B. T., Ferrante, R. J., Kowall, N. W., Srivastava, R., Roy, D. S., Rosen, B. R., & Beal, M. F.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- Beal, M. Flint
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1993-01
- Volume
- 60
- Issue
- 1
- Pages
- 356-359
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1983729920
- Cited by
- 367
- References
- 16
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 11 · 2015: 3 · 2014: 11 · 2013: 6 · 2012: 10
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (16367)
- National Institute of Neurological Disorders and Stroke (NS10828)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- Huntington's disease, 3-nitropropionic acid, striatum, age-related susceptibility, mitochondrial toxins, dendritic changes, lactate, energy metabolism, excitotoxicity, neurodegeneration
- MeSH terms
- Adenosine Triphosphate, Aging, Corpus Striatum, Lactates, Mitochondria, Neurotoxins, Nitro Compounds, Propionates, Lactic Acid, In Vitro Techniques
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