The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner
2011

MAM and Its Effects on Brain Pathways Related to Neurodegenerative Disease and Cancer

Sample size: 8 publication 10 minutes Evidence: moderate

Author Information

Author(s): Glen E. Kisby, Rebecca C. Fry, Michael R. Lasarev, Theodor K. Bammler, Richard P. Beyer, Mona Churchwell, Daniel R. Doerge, Lisiane B. Meira, Valerie S. Palmer, Ana-Luiza Ramos-Crawford, Xuefeng Ren, Robert C. Sullivan, Terrance J. Kavanagh, Leona D. Samson, Helmut Zarbl, Peter S. Spencer

Primary Institution: Oregon Health & Science University

Hypothesis

The DNA-damaging properties of MAM activate molecular networks associated with the degeneration of post-mitotic neurons in neurodegenerative disease.

Conclusion

MAM induces persistent DNA damage and modulates signaling pathways in the brains of mice, which may relate to neurodegenerative diseases like ALS and Alzheimer's.

Supporting Evidence

  • MAM treatment resulted in DNA damage in the brains of adult mice.
  • Significant differences in gene expression were observed between wild-type and Mgmt−/− mice.
  • Pathways associated with cancer and neurodegeneration were activated in response to MAM.
  • Persistent DNA damage was linked to changes in neurotransmitter signaling pathways.

Takeaway

MAM, a toxin from a plant, can hurt brain cells and might be linked to diseases like Alzheimer's and ALS.

Methodology

Adult C57BL6 wild-type and Mgmt−/− mice were treated with a single systemic dose of MAM, and DNA damage and gene expression were analyzed.

Potential Biases

Potential bias in gene expression analysis due to the use of different laboratories.

Limitations

The study primarily used mouse models, which may not fully replicate human responses.

Participant Demographics

C57BL6 wild-type and Mgmt−/− mice.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.01

Digital Object Identifier (DOI)

10.1371/journal.pone.0020911

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication