|Document Type:||Journal Article|
|Title:||Chronic low-level domoic acid exposure alters gene transcription and impairs mitochondrial function in the CNS|
|Author:||Emma M. Hiolski, Preston Kendrick, Elizabeth Rose Frame, Mark S. Myers, Theo K. Bammler, Richard P. Beyer, Frederico M. Farin, D. Smith, David J. Marcinek, K. A. Lefebvre|
|Keywords:||domoic acid,seafood toxin,chronic exposure,harmful algal bloom,chronic exposure,algal toxin,biomarkers|
Domoic acid is an algal-derived seafood toxin that functions as a glutamate agonist and exerts excitotoxicity via overstimulation of glutamate receptors (AMPA, NMDA) in the central nervous system (CNS). At high (symptomatic) doses, domoic acid is well-known to cause seizures, brain lesions and memory loss; however, a significant knowledge gap exists regarding the health impacts of repeated low-level (asymptomatic) exposure. Here, we investigated the impacts of low-level repetitive domoic acid exposure on gene expression and mitochondrial function in the vertebrate CNS using a zebrafish model in order to: 1) identify transcriptional biomarkers of exposure; and 2) examine potential pathophysiology that may occur in the absence of overt excitotoxic symptoms. We found that genes and biological functions related to neurological function and development were significantly altered, and that asymptomatic exposure impaired mitochondrial function. Interestingly, the transcriptome response was highly-variable across the exposure duration (36 weeks), with little to no overlap of specific genes across the six exposure time points (2, 6, 12, 18, 24, and 36 weeks). Moreover, there were no apparent similarities at any time point with the gene expression profile exhibited by the glud1 mouse model of chronic moderate excess glutamate release. These results suggest that although the fundamental mechanisms of toxicity may be similar, gene responses to domoic acid exposure do not extrapolate well between different exposure durations. However, the observed impairment of mitochondrial function suggests that repetitive low-level exposure does have fundamental cellular level impacts that could contribute to chronic health consequences.
|Theme:||Sustainable, safe and secure seafood for healthy populations and vibrant communities|
Provide scientific support to ensure safe seafood for healthy populations and characterize how human activities and climate affect risks from pathogens, chemical contaminants and biotoxins