The Transcriptomic and Proteomic Molecular Signatures of Equine Multiple-System Neuropathy (Grass Sickness)

Equine grass sickness (EGS or equine dysautonomia) is a predominantly fatal multi-system neuropathy affecting grazing horses, likely caused by a neurotoxic phospholipase A2 (nPLA2) derived from a plant or microorganism. We studied neuronal tissue gene and protein expression patterns in EGS to elucidate the possible mechanisms of neurotoxicity and neurodegeneration. Tissue from the cranial cervical ganglion of eight EGS horses and six controls was examined histologically and used for transcriptomic analysis. These transcriptomic data were compared with previously published EGS-related proteomic datasets from different horses. Results were visualized using the network analysis tool BioLayout and Ingenuity Pathway Analysis. The cranial cervical ganglia from all affected horses showed pathology typical of EGS. They also showed distinct gene and protein expression profiles that were different from the controls. The EGS signature consisted ofreduced expression of genes and proteins involved in neurological function (including ion-channel and synaptic-function genes and genes encoding mitochondrial proteins) and increased expression of genes and proteins indicative of cellular stress, cell death and inflammation. This signature likely reflects more generalized neurodegeneration. This study thus improves our understanding of the molecular changes likely to be associated with a neurotoxic neurodegenerative process.