Selective vulnerability of the posterior visual pathway to acute cuprizone treatment 

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Presenter Information(s)

Kate Brassell

Abstract or Description

Multiple sclerosis (MS) is a chronic disease characterized by the degradation of myelin sheaths in the brain and spinal cord, leading to motor, sensory, visual, and cognitive deficits. Myelin sheaths are produced by oligodendrocytes and facilitate rapid communication between neurons. In the laboratory setting, we model myelin sheath degeneration by administering the drug cuprizone to mice, and we monitor the loss and repair of myelin over time in the living animal using in vivo two-photon microscopy. Using this approach, we observed myelin loss in the visual cortex but we are unable to quantify demyelination in the rest of the visual pathway. I hypothesized that acute cuprizone administration in mice would lead to overt myelin loss across the visual pathway in the brain. To test our hypothesis, mice were fed a cuprizone-supplemented diet for three weeks and brain tissue was analyzed via immunohistochemistry, focusing on key regions in the visual pathway. While the optic nerve and a thalamic relay center (dLGN) showed no myelin loss, regions in the rear of the visual pathway were notably affected, indicating acute cuprizone treatment promotes posterior-biased myelin loss in the visual pathway. This research will inform studies evaluating therapeutic strategies to promote myelin repair in MS and other demyelinating diseases and specifically provide insights into how demyelination in the posterior visual pathway affects vision of patients with MS. 

Mentor

Ethan Hughes, PhD