Bovine hepatic differential gene expression in response to perennial ryegrass staggers

Abstract

>‘Perennial ryegrass staggers’ is a neurological condition characterised by muscular tremors and ataxia in livestock that ingest the indole diterpene lolitrem B from endophyte-infected perennial ryegrass. While the neurotoxic mechanism of action of ryegrass staggers has been defined, little is known about metabolic and other molecular processes that lolitrem B may affect in livestock. The objective of this study was to characterise differential gene expression in the liver of animals fed lolitrem B-containing feed over an extended period of time. Eighteen steers were fed one of three rations (n=6/group) containing lolitrem B (247, 1,554 or 2,256 μg/kg (dry matter basis)) over 64 days in a double-blind study. Microarray and confirmatory qPCR were performed to evaluate the hepatic gene expression profile from biopsies taken on days 0 and 64. Widespread perturbation of gene expression was observed in all groups receiving lolitrem B, with a total of 152 differential genes identified (false discovery rate ≤0.05). This suggests that chronic exposure to lolitrem B, even at levels below the current threshold of toxicity (2,000 μg/kg lolitrem B), can perturb many genes, biological processes and pathways. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that many of these genes were categorised under lipid/steroid biosynthesis/metabolism and oxidation-reduction. Specifically, genes involved in the biosynthesis pathway of ceramide, a sphingolipid molecule (ACSS2,LASS6 andSCD) and changes in neurosignaling through alteration of nitric oxide synthase activity (ARG1 andGPX4) were up-regulated. Future work should focus on the overall balance between ceramide and its metabolites and antioxidants/oxidants in a variety of body matrices in animals with perennial ryegrass staggers, to determine how these compounds contribute to the overall etiology of this disease.