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Cited by 34Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingActinomycetales infections and treatment

Neuroinvasive Nocardia asteroides GUH-2 Induces Apoptosis in the Substantia Nigra in Vivo and Dopaminergic Cells in Vitro

Tam, S·2002·Experimental Neurology
DOI 10.1006/exnr.2002.8012
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Abstract

Neurodegenerative diseases such as Parkinson's disease are increasingly prevalent in the aging population worldwide. The causes of these disorders are unknown, but many studies have suggested that the etiology is likely multifactorial and may involve exposure to something in the environment combined with the normal aging process. Nocardia asteroides are bacteria commonly found in the soil, and neuroinvasive strains of nocardiae have been described. N. asteroides strain GUH-2 invades the brains of experimentally infected animals and selectively affects dopaminergic neurons of the substantia nigra (SN), causing an L-DOPA-responsive movement disorder resembling parkinsonism. Furthermore, dopaminergic neurons undergo morphological changes characteristic of apoptosis following nocardial infection. Apoptosis has been implicated in dopaminergic neuronal dropout in Parkinson's patients as well as other parkinsonian models. Thus, in this study, in vivo and in vitro models were utilized to measure the ability of GUH-2 to induce the apoptotic death of dopaminergic cells. Following infection with GUH-2, dopaminergic apoptotic cells were identified in the SN of animals by in situ end labeling, which detects DNA fragmentation, combined with fluorescent immunolabeling of tyrosine hydroxylase-positive cells. In addition, apoptosis was observed in PC12 cell cultures incubated with GUH-2 by both in situ end labeling and the annexin V assay, which detects externalization of phosphatidylserine of the plasma membrane, indicating apoptotic death. Based on the results of these studies, it appears that experimental infection with N. asteroides provides a general model for studying apoptosis in parkinsonian disorders.

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  • Mice injected with Nocardia astroides can cause Parkinson's like symptoms and respond to dopamine therapy, and N. astroides strain GUH-2 can cause apoptosis of dopamine neurons.

    “Mice injected with Nocardia astroides (N. astroides, a human pathogen of the phylum Actinobacteria) can cause Parkinson’s like symptoms and respond to dopamine therapy, and N. astroides strain GUH-2 can cause apoptosis of dopamine neurons (Tam et al. 2002).”

    From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Tam et al. 2002

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Authors
Tam, S.
Affiliations
University of California, Davis (US)
Corresponding author
Tam, S
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2002-10
Volume
177
Issue
2
Pages
453-460
ISSN
0014-4886 (ISSN-L)
DOI
10.1006/exnr.2002.8012
OpenAlex
W2071337078
Cited by
34
References
36
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2014: 2 · 2013: 1
FWCI
1.33
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute for Health and Care Research
  • Institute of Environmental Science and Research
  • National Institute of Environmental Research
  • National Institutes of Health (5r01ai042144-02)
  • University of California, Davis
  • National Institute of Allergy and Infectious Diseases (R01-AI-42144)
  • National Institute of Environmental Health Sciences (R01ES010793)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Health Sciences › Medicine › Microbiology › Actinomycetales infections and treatment
Keywords
Nocardia asteroides, Parkinson's disease, substantia nigra, dopaminergic neurons, apoptosis, PC12 cells, tyrosine hydroxylase, parkinsonism, DNA fragmentation, phosphatidylserine exposure, bacterial infection model
MeSH terms
Animals, Bacterial Adhesion, Cell Differentiation, Cells, Cultured, Disease Models, Animal, Dopamine, Female, Flow Cytometry, Mice, Inbred BALB C, Neurons, Nocardia asteroides, Nocardia Infections, Phosphatidylserines, Substantia Nigra, Tyrosine 3-Monooxygenase, PC12 Cells, Apoptosis, Microscopy, Confocal, Parkinsonian Disorders, Mice, Rats, DNA Fragmentation

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