Cited by 368Genetic Neurodegenerative DiseasesMitochondrial Function and PathologyParkinson's Disease Mechanisms and Treatments

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Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid

Brouillet, Emmanuel, Jenkins, Bruce G., Hyman, Bradley T., Ferrante, Robert J., Kowall, Neil W., Srivastava, Rachana, Roy, Deborah Samanta, Rosen, Bruce R., Beal, M. Flint·1993·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.1993.tb05859.x

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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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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
ORCID: Brouillet, Emmanuel
Hyman, Bradley T.
Kowall, Neil W.
Rosen, Bruce R.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 1993-01
Volume: 60
Issue: 1
Pages: 356-359
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.1993.tb05859.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5025 d)
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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Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid

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