Abstract
Domoic acid is a neurotoxin produced by algal species including Pseudo-nitzschia. California sea lions (Zalophus californianus) ingest the toxin when foraging on planktivorous fish and acute toxicity is a common cause of neurologic disease.2 A second neurological syndrome characterized by epilepsy also occurs as a chronic consequence of previous exposure to the toxin.1 We investigated both cardiac and reproductive affects as additional sequellae to previous toxin exposure.
Domoic acid affected sea lions that died in rehabilitation with neurological signs were examined histologically for concurrent cardiac lesions. A degenerative cardiomyopathy was detected in 43% of 235 cases that varied from acute to chronic active, varied in severity, and was distinguishable from other heart pathology according to lesion morphology and distribution. Microscopically, the primary lesion was cardiomyocyte vacuolar degeneration and loss with adipocyte replacement. Lesions seemed associated with the conducting system, starting at the base of the interventricular septum adjacent to the atrioventricular node and progressed distally. Identification of the conducting system was confirmed by immunohistochemistry for Protein Gene Product 9.5 antibody. The cardiomyopathy was associated with cleaved caspase 3 immunoreactivity, indicating apoptosis contributes to the pathogenesis. Serum troponin levels were investigated as potential biomarkers of cardiac damage (n = 34), but no consistent associations between extent and severity of cardiac lesions and serum troponin levels were found.
To investigate the role of domoic acid in reproductive failure in free-ranging sea lions, 67 prematurely born or aborted pups were examined on the on San Miguel Island sea lion rookery and compared to those dying in rehabilitation as offspring of domoic acid affected dams. Both Pseudo-nitzschia spp. and domoic acid were detected in the environment of the rookery and in sea lion feces, and the toxin was also present in 17% of pup samples tested. The primary histopathologic lesion in fetuses with measurable domoic acid concentrations was brain edema, a common finding, and in some cases the only lesion, observed in pups born aborted from intoxicated females in rehabilitation. Various bacteria were cultured from aborted fetal tissues associated with compatible histopathology to suggest that ascending infections of the reproductive tract also played a role in reproductive failure. Organochlorine levels in dead pup blubber samples were below those measured in brains of full term pups previously examined on San Miguel Island. These data suggest that domoic acid is likely to be playing at least a contributory role in reproductive failure of free-ranging sea lions. Our results indicate that domoic acid toxicity results in additional disease syndromes beyond central neurologic disease that contribute to morbidity and mortality of California sea lions.
acknowledgments
We would like to acknowledge our many coauthors and collaborators R. DeLong, E. Wheeler, G. Ylitalo, S. Bargu, M. Silver, T. Leighfield, F. Van Dolah, G. Langlois, I. Sidor, J. L. Dunn, C. Cross, R. Mueller, C. Kreuder-Johnson, S. Gill and T. Spraker. This study was supported by funds from the U.S. National Marine Fisheries Service, Oceans and Human Health Initiative grant number NA04OAR4600200 and through a Morris Animal Foundation Fellowship Training grant number D05ZO-401.
References
1. Goldstein T, JAK Mazet, TS Zabka, G Langlois, KM Colegrove, M Silver, S Bargu, F Van Dolah, T Leighfield, PA Conrad, J Barakos, DC Williams, S Dennison, MA Haulena, FMD Gulland. 2008. Novel symptomatology and changing epidemiology of domoic acid toxicosis in California sea lions (Zalophus californianus): an increasing risk to marine mammal health. Proceedings of the Royal Society B 275: 267-276.
2. Scholin CA, F Gulland, GJ Doucette, S Benson, M Busman, FP Chavez, J Cordaro, R Delong, A De Vogelaere, J Harvey, M Haulena, K Lefebvre, T Lipscomb, S Loscutoff, LJ Lowenstine, R Marin 3rd, PE Miller, WA McLellan, P. Moeller, CL Powell, T Rowles, P Silvagni, M Silver, T Spraker, V Trainer, FM Van Dolah. 2000. Mortality of sea lions along the central California coast linked to a toxic diatom bloom. Nature 403: 80-84.