Zebrafish oligodendrocyte lineage cells use the postsynaptic protein Gephyrin to myelinate GABAergic axons and limit myelin sheath growth.

Equine grass sickness (EGS or equine dysautonomia) is a predominantly fatal multiple-system neuropathy affecting grazing horses. It occurs throughout the UK and Northern Europe with a mortality rate between 50% and 80% []. Although there is no equivalent condition in humans, an apparently identical disease occurs in cats, dogs, hares, rabbits, llamas and possibly sheep [,,,,,,]. The classic pathology in cases of EGS is widespread chromatolysis of enteric, parasympathetic and postganglionic sympathetic neurons, general visceral efferent and general somatic efferent lower motor neurons in the brainstem and general somatic efferent lower motor neurons in the spinal cord [,]. The clinical signs of EGS largely reflect dysfunction of enteric and autonomic neurons and include dysphagia, generalized ileus, sweating, salivation, ptosis, tachycardia, and rhinitis sicca, which can range from mild crusting of the mucous membranes of the nasal cavity to severe ulcerative lesions (reviewed in []). EGS is subdivided into acute, sub-acute and chronic forms according to the severity and duration of the clinical signs. The acute and sub-acute forms are associated with 100% mortality, whereas the chronic form has a survival rate approximating 50%. While the etiology of EGS remains unconfirmed, recent studies identified ultrastructural abnormalities in the skeletal muscle neuromuscular junctions that are consistent with the actions of a neurotoxic phospholipase A2 (nPLA2), presumably derived from plants or soil or resident intestinal microorganisms [,,]. Ultrastructural findings suggest that the lesion in EGS primarily involves the loss of the Golgi apparatus of specific neuronal populations []. We previously reported widespread changes in the proteome of the cranial (superior) cervical ganglion (CCG) of horses with EGS [], including disruption of pathways involving proteins associated with protein misfolding responses, akin to those identified in human neurodegenerative diseases. Analysis of the proteome shows the functional endpoints of the disease state. Since this can be achieved through transcriptional, translational or post-translational mechanisms, we were interested in determining the gene expression changes associated with terminal neuropathy that would precede these proteomic changes. Hence, the aim of the present study was to evaluate gene expression in the CCG, using a transcriptome-wide approach, to elucidate gene-level responses to the ongoing neurodegenerative condition in EGS. We also updated the previous proteomic data to identify proteins not annotated at the time of the original analysis and compared these results with the transcriptomic analysis. This study offers an opportunity to analyze transcriptomic and proteomic alterations in a naturally occurring neurodegenerative disease. Sample collection and analysis was approved by the University of Edinburgh Veterinary Ethical Review Committee. Samples were collected at necropsy from horses that were subjected to euthanasia on humane grounds, by intravenous injection of a combination of quinalbarbitone and cinchocaine (Somulose, Dechra, Shrewsbury, UK), with the horse owners’ informed consent.