Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Published

May 28, 2024

Author(s)

Gautam Ghosh, Ben Neely, Alison Bland, Emily Whitmer, Cara Field, Pádraig Duignan, Michael Janech

Abstract

Since 1998, California sea lion (Zalophus californianus) stranding events associated with domoic acid toxicosis have consistently increased. Currently there are no practical non-lethal clinical tests for the diagnosis of domoic acid toxicosis (DAT) that can be utilized in a large-scale rehabilitation facility. Proteomic analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid from stranded California sea lions with acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005 protein families were identified experiment-wide (FDR < 0.01). Of these proteins, 83 were significantly different in abundance across the three groups (adj. p < 0.05). Cytoplasmic malate dehydrogenase (MDH1), 5'-3' exonuclease PLD3, disintegrin and metalloproteinase domain-containing protein 22 (ADAM22), 14-3-3 protein gamma (YWHAG), neurosecretory protein VGF, and calsyntenin-1 (CLSTN1) were able to discriminate California sea lions with or without DAT (ROC > 0.75). Immunoglobulin kappa light chain-like (IGKV2D-28), receptor-type tyrosine-phosphatase F (PTRPF), kininogen-1 (KNG1), prothrombin (F2), and beta-synuclein (SNCB) were able to discriminate acute DAT from chronic DAT (ROC > 0.75). Interestingly, proteins involved in alpha synuclein deposition were over-represented as classifiers of DAT and many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions, as well as markers to discriminate between acute or chronic DAT, and should be considered priority for future validation studies as biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD041356 (http://proteomecentral.proteomexchange.org/dataset/PXD041356).

Citation

ACS Journal of Proteome Research

Pub Type

Journals

Download Paper

https://doi.org/10.1021/acs.jproteome.4c00103

Local Download

Keywords

toxicosis, marine mammal, neurodegeneration, brain, domoic acid

Citation

Ghosh, G. , Neely, B. , Bland, A. , Whitmer, E. , Field, C. , Duignan, P. and Janech, M. (2024), Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus), ACS Journal of Proteome Research, [online], https://doi.org/10.1021/acs.jproteome.4c00103, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=957220 (Accessed June 30, 2024)