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Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease
Glen E Kisby1, Peter S Spencer2
1College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Lebanon, OR, United States.
Frontiers in Neuroscience
|December 20, 2021
Summary
Exposure to cycad genotoxin methylazoxymethanol (MAM) during development may trigger neurodegenerative diseases like ALS/PDC. This genotoxin causes DNA damage and alters gene expression, potentially leading to conditions such as Alzheimer's and schizophrenia.
Area of Science:
- Neuroscience
- Toxicology
- Genetics
Background:
- Western Pacific ALS/PDC is a rare neurodegenerative disorder linked to cycad toxin exposure.
- Methylazoxymethanol (MAM), a cycad genotoxin, causes developmental brain abnormalities in animal models.
Purpose of the Study:
- To investigate the role of MAM in neurodevelopment and neurodegeneration.
- To explore the hypothesis that early-life genotoxic exposure contributes to neurodegenerative diseases.
Main Methods:
- Administration of MAM to rodents at different developmental stages.
- Analysis of histological, neurophysiological, and behavioral deficits.
- Examination of DNA damage, repair, tau expression, and brain transcriptional changes.
Main Results:
- MAM exposure during development models schizophrenia, epilepsy, or ataxia.
- MAM induces DNA damage and repair patterns associated with increased tau expression.
- Transcriptional changes in the brain parallel those in human ALS and Alzheimer's disease.
Conclusions:
- Early-life MAM exposure may trigger molecular events leading to neurodegeneration.
- Genotoxic agents could play a role in the pathogenesis of sporadic neurodegenerative diseases.
- Further research is needed to explore the link between environmental toxins and neurodegeneration.
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