Neuropathology and brain atrophy in Wolfram syndrome

Abstract

Wolfram syndrome is a rare autosomal recessive disease. It is caused by mutations in the WFS1 gene. The symptoms appear early in childhood including at first diabetes mellitus followed by optic nerve atrophy. Wolfram syndrome has currently no cure. Studies with patients have shown that most of atrophy occurs in the brain stem and cerebellum. Our work in the laboratory with the mouse model of WS has shown that the trigeminal nerve shows a critical role in disease progression. The aim of this work was to characterize very early changes in pathology in a mouse model of WS. In this thesis, I demonstrate how severely affected these mice are, by the time of initial brain changes detected using magnetic resonance imaging (MRI). The results showed that very young mice had a reduction in the cerebellar volume. The trigeminal tract size was also reduced. The used methods help to better understand early disease and to ultimately pinpoint earliest neurodegenerative changes for better management of these patients.