title: Proteomic analysis of cerebrospinal fluid in California sea lions (Zalophus californianus) with domoic acid toxicosis identifies proteins associated with neurodegeneration.
abstract: Proteomic studies including marine mammals are rare, largely due to the lack of fully sequenced genomes. This has hampered the application of these techniques toward biomarker discovery efforts for monitoring of health and disease in these animals. We conducted a pilot label-free LC-MS/MS study to profile and compare the cerebrospinal fluid from California sea lions with domoic acid toxicosis (DAT) and without DAT. Across 11 samples, a total of 206 proteins were identified (FDR<0.1) using a composite mammalian database. Several peptide identifications were validated using stable isotope labeled peptides. Comparison of spectral counts revealed seven proteins that were elevated in the cerebrospinal fluid from sea lions with DAT: complement C3, complement factor B, dickkopf-3, malate dehydrogenase 1, neuron cell adhesion molecule 1, gelsolin, and neuronal cell adhesion molecule. Immunoblot analysis found reelin to be depressed in the cerebrospinal fluid from California sea lions with DAT. Mice administered domoic acid also had lower hippocampal reelin protein levels suggesting that domoic acid depresses reelin similar to kainic acid. In summary, proteomic analysis of cerebrospinal fluid in marine mammals is a useful tool to characterize the underlying molecular pathology of neurodegenerative disease. All MS data have been deposited in the ProteomeXchange with identifier PXD002105 (http://proteomecentral.proteomexchange.org/dataset/PXD002105).
authors.affiliation: Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Neely
authors.affiliation: The Marine Mammal Center, Sausalito, CA, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Soper
authors.affiliation: The Marine Mammal Center, Sausalito, CA, USA.
authors.forename: Frances M D
authors.initials: FM
authors.lastname: Gulland
authors.affiliation: Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: P Darwin
authors.initials: PD
authors.lastname: Bell
authors.affiliation: Marine Biomedicine and Environmental Sciences Center, Medical University of South Carolina, Charleston, SC, USA.|Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.|Department of Veterans' Affairs, Research Service, Charleston, SC, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Kindy
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Arthur
authors.affiliation: Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA.|Marine Biomedicine and Environmental Sciences Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Janech
mesh_terms: D000818:Animals; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D040901:Proteomics; D000091042:Reelin Protein; D046070:Sea Lions / Q000235:genetics / Q000378:metabolism*
chemical_list: D000091042:Reelin Protein; C000717128:Reln protein, mouse; C012301:domoic acid; D007608:Kainic Acid
keywords: Animal proteomics; Label-free; Marine mammal; Neuron cell adhesion molecule; Reelin; Spectral count