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Exposure to mitochondrial genotoxins and dopaminergic neurodegeneration in Caenorhabditis elegans.

Publication ,  Journal Article
González-Hunt, CP; Leung, MCK; Bodhicharla, RK; McKeever, MG; Arrant, AE; Margillo, KM; Ryde, IT; Cyr, DD; Kosmaczewski, SG; Hammarlund, M; Meyer, JN
Published in: PloS one
January 2014

Neurodegeneration has been correlated with mitochondrial DNA (mtDNA) damage and exposure to environmental toxins, but causation is unclear. We investigated the ability of several known environmental genotoxins and neurotoxins to cause mtDNA damage, mtDNA depletion, and neurodegeneration in Caenorhabditis elegans. We found that paraquat, cadmium chloride and aflatoxin B1 caused more mitochondrial than nuclear DNA damage, and paraquat and aflatoxin B1 also caused dopaminergic neurodegeneration. 6-hydroxydopamine (6-OHDA) caused similar levels of mitochondrial and nuclear DNA damage. To further test whether the neurodegeneration could be attributed to the observed mtDNA damage, C. elegans were exposed to repeated low-dose ultraviolet C radiation (UVC) that resulted in persistent mtDNA damage; this exposure also resulted in dopaminergic neurodegeneration. Damage to GABAergic neurons and pharyngeal muscle cells was not detected. We also found that fasting at the first larval stage was protective in dopaminergic neurons against 6-OHDA-induced neurodegeneration. Finally, we found that dopaminergic neurons in C. elegans are capable of regeneration after laser surgery. Our findings are consistent with a causal role for mitochondrial DNA damage in neurodegeneration, but also support non mtDNA-mediated mechanisms.

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Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2014

Volume

9

Issue

12

Start / End Page

e114459

Related Subject Headings

  • Paraquat
  • Oxidopamine
  • Nerve Degeneration
  • Mutagens
  • Mitochondria
  • General Science & Technology
  • Dopaminergic Neurons
  • Dopamine Agents
  • Dopamine
  • DNA, Mitochondrial
 

Citation

APA
Chicago
ICMJE
MLA
NLM
González-Hunt, C. P., Leung, M. C. K., Bodhicharla, R. K., McKeever, M. G., Arrant, A. E., Margillo, K. M., … Meyer, J. N. (2014). Exposure to mitochondrial genotoxins and dopaminergic neurodegeneration in Caenorhabditis elegans. PloS One, 9(12), e114459. https://doi.org/10.1371/journal.pone.0114459
González-Hunt, Claudia P., Maxwell C. K. Leung, Rakesh K. Bodhicharla, Madeline G. McKeever, Andrew E. Arrant, Kathleen M. Margillo, Ian T. Ryde, et al. “Exposure to mitochondrial genotoxins and dopaminergic neurodegeneration in Caenorhabditis elegans.PloS One 9, no. 12 (January 2014): e114459. https://doi.org/10.1371/journal.pone.0114459.
González-Hunt CP, Leung MCK, Bodhicharla RK, McKeever MG, Arrant AE, Margillo KM, et al. Exposure to mitochondrial genotoxins and dopaminergic neurodegeneration in Caenorhabditis elegans. PloS one. 2014 Jan;9(12):e114459.
González-Hunt, Claudia P., et al. “Exposure to mitochondrial genotoxins and dopaminergic neurodegeneration in Caenorhabditis elegans.PloS One, vol. 9, no. 12, Jan. 2014, p. e114459. Epmc, doi:10.1371/journal.pone.0114459.
González-Hunt CP, Leung MCK, Bodhicharla RK, McKeever MG, Arrant AE, Margillo KM, Ryde IT, Cyr DD, Kosmaczewski SG, Hammarlund M, Meyer JN. Exposure to mitochondrial genotoxins and dopaminergic neurodegeneration in Caenorhabditis elegans. PloS one. 2014 Jan;9(12):e114459.

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2014

Volume

9

Issue

12

Start / End Page

e114459

Related Subject Headings

  • Paraquat
  • Oxidopamine
  • Nerve Degeneration
  • Mutagens
  • Mitochondria
  • General Science & Technology
  • Dopaminergic Neurons
  • Dopamine Agents
  • Dopamine
  • DNA, Mitochondrial