Profiling neurodegeneration of sensory systems in multiple sclerosis

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Neurodegeneration in multiple sclerosis (MS) follows a particular spatial distribution with some brain regions and neuronal subtypes being more affected than others. The visual and olfactory system are commonly disturbed in MS and its animal model experimental autoimmune encephalomyelitis (EAE), resulting in sensory deficits. However, the underlying intrinsic properties that put neurons at risk for degeneration are still incompletely understood. As sensory systems are ideal representative regions to identify shared pathways that determine neuronal injury during inflammation, we propose to leverage olfactory bulb and retina samples to explore the principles of differential neuronal vulnerability in MS. Therefore, we will analyze transcriptional profiles of neuronal nuclei from both human MS tissue and different stages of EAE mouse models in comparison to appropriate controls. By using droplet based single cell RNA sequencing we will identify vulnerable neuron subtypes and use neuronal in vitro systems to explore targetable candidates to reinforce susceptible neuronal populations. This approach will advance our understanding of neuronal loss in MS and deliver new therapeutic angles to counteract neurodegeneration.