Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells
2008

Rotenone Treatment Mimics Early Parkinson's Disease in Neural Cells

publication Evidence: moderate

Author Information

Author(s): Borland M Kathleen, Trimmer Patricia A, Rubinstein Jeremy D, Keeney Paula M, Mohanakumar KP, Liu Lei, Bennett James P Jr

Primary Institution: Center for the Study of Neurodegenerative Diseases and Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Virginia, Charlottesville, Virginia, USA

Hypothesis

Chronic, low-dose rotenone exposure will reproduce Lewy neurites and mitochondrial dysfunction observed in early stages of Parkinson's disease.

Conclusion

Rotenone treatment of differentiated SH-SY5Y cells leads to neuritic retraction and partial cell death, mimicking early Parkinson's disease pathology without forming Lewy bodies.

Supporting Evidence

  • 60% of cells died after 21 days of rotenone treatment.
  • Mitochondrial movement velocities were significantly reduced by 8 days of rotenone exposure.
  • Gene expression analysis showed a majority of genes were under-expressed in treated cells.
  • Rotenone treatment induced the formation of neuritic swellings resembling Lewy neurites.

Takeaway

When we give a chemical called rotenone to special brain cells, they start to die and change shape like the cells in people with Parkinson's disease.

Methodology

Differentiated SH-SY5Y neuroblastoma cells were treated with 50 nM rotenone for up to 21 days to assess cell death, mitochondrial movement, and gene expression changes.

Limitations

The study used a neuroblastoma cell line rather than primary neurons, which may affect the generalizability of the findings.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1750-1326-3-21

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