In vivo pathogenesis of neurodegeneration in multiple sclerosis

Abstract

Here, I want to discuss how in vivo microscopy techniques can be used to better understand the emergence of neurodegeneration during CNS inflammation.

To illustrate this I will discuss two lines of work. First I will present our recent insights into the in vivo pathogenesis of immune-mediated axon damage in an animal model of multiple sclerosis. I will highlight how in vivo imaging can help us reveal how immune cells damage axons in the inflamed spinal cord. In particular I will focus on recent insights that explore the emergence of mitochondrial pathology in neuroinflammatory lesions and identify a dysbalance of the TCA cycle as a critical checkpoint for axonal energy homeostasis that can be targeted therapeutically. In the second part of my talk I will focus on the structural and functional pathology of neurons in the inflamed gray matter. Here I will focus on the role of synaptic pathology, the mechanisms that induce it and its relation to altered neuronal function.