An algal toxin leaves traces in the brain and other tissues of rodents after oral consumption, according to a study by researchers from the National Toxicology Program (NTP). The findings, published Dec. 15 in the journal Toxicology and Applied Pharmacology, provide much-needed data for designing and interpreting future toxicology studies.
Algae are microscopic organisms commonly found in aquatic environments. Sometimes their excessive growth, known as an algal bloom, results in the release of toxins that could pose a threat to human health.
One such toxin is beta-N-methylamino-l-alanine (L-BMAA), which some speculate may contribute to human neurodegenerative diseases. This amino acid is produced by cyanobacteria, or blue-green algae, in fresh and marine waters around the globe. People may potentially be exposed to L-BMAA by consuming contaminated water, supplements, or food items such as shellfish.
“NTP wanted to find out whether L-BMAA gets absorbed following oral exposure, whether it is distributed to tissues including the brain, and whether it accumulates in the brain,” said first author Suramya Waidyanatha, Ph.D., leader of the NTP Chemistry and Absorption, Distribution, Metabolism, and Excretion (ADME) Resources Group.
Previous studies in humans have suggested that L-BMAA may contribute to the development of neurodegenerative diseases. For example, exposure to this toxin has been linked to Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, or Lou Gehrig’s disease.
Investigating the health risk
NTP, a federal interagency program headquartered at NIEHS, has taken notice of these troublesome findings. In 2008, NTP selected L-BMAA for toxicological assessment based on its potential widespread occurrence in the environment and evidence that it is a neurotoxin.
Researchers from NTP and Lovelace Respiratory Research Institute collaborated on the new study to better understand the potential health risks of L-BMAA in humans. The team carried out the first comprehensive study to examine the distribution and metabolism of this toxin in animal models following oral exposure.
Significant accumulation, slow elimination
Waidyanatha and her collaborators found that following oral consumption, L-BMAA was well absorbed by rodents and distributed to all of the tissues examined. Moreover, L-BMAA was slowly eliminated from blood and tissues over the following days and weeks. Repeated exposure and higher doses increased L-BMAA levels in various tissues.
However, L-BMAA accumulation was not higher in the brain than in other tissues. Nor did L-BMAA become incorporated into brain proteins at significant levels. This finding challenges a prevailing hypothesis about how L-BMAA might induce neurodegeneration in humans. For now, the potential causal relationship between L-BMAA exposure and neurodegenerative disease in humans remains uncertain.
“We believe the findings in these studies will prove useful for investigators designing additional toxicology studies regarding L-BMAA,” Waidyanatha said. “NTP will continue to engage with other individuals in the public health and research communities to discuss scientific areas of interest regarding L-BMAA and other cyanobacterial toxins.”
Citation: Waidyanatha S, Ryan K, Sanders JM, McDonald JD, Wegerski CJ, Doyle-Eisle M, Garner CE. 2018. Disposition of Beta-N-methylamino-l-alanine (L-BMAA), a neurotoxin, in rodents following a single or repeated oral exposure. Toxicol Appl Pharmacol 339:151–160.
(Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)