Benjamin Neely Student Research Day Abstract
Proteomic Analysis Of Cerebral Spinal Fluid Reveals Candidate Biomarkers Of Domoic Acid Toxicosis In California Sea Lions, Benjamin A Neely1, Jennifer Soper2, Frances M D Gulland2, John M Arthur3, Michael G Janech3; 1Nephrology, MUSC, 2The Marine Mammal Center, 3Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC.
Domoic acid toxicosis (DAT) is a major cause of California sea lion (Zalophus californianus) strandings along the west coast of the United States. Domoic acid is a potent neurotoxin produced by some marine diatoms, which causes hippocampal atrophy and necrosis as a result of excessive stimulation of AMPA-kainate and NMDA receptors, and is rapidly cleared from the body. DAT is classified as acute or chronic, with the former recovering over time and the latter progressing to status epilepticus. Currently markers of DAT are limited and inconclusive; therefore by developing markers of DAT, diagnosis and treatment could be greatly facilitated. For this reason we evaluated whether protein differences exist in the cerebral spinal fluid (CSF) that could be utilized as markers of DAT. CSF samples from 11 sea lions [3 without DAT, 2 diagnosed with acute-DAT and 6 with chronic-DAT] were acquired from The Marine Mammal Center and proteins were digested with trypsin for analysis by tandem mass spectrometry. Data were searched using Mascot against a mammalian database, with identifications supported by Scaffold. We identified 182 experiment-wide proteins with a protein false discovery rate of <0.1%. Relative protein abundance was estimated for comparison by spectral counts across all samples and differences were detected using a Wilcoxon rank-sum test. Six proteins were significantly different (p<0.05) between non-DAT and DAT animals, five of which were higher in animals with DAT. Interestingly, Dickkopf-3 and Gelsolin were elevated in sea lions with DAT. Both of these proteins have been implicated in the progression of Alzheimer’s disease, suggesting that DAT and Alzheimer’s may share common features. Future studies to qualify these proteins as markers of DAT are ongoing. ONR N00014-08-1-0341