Grant: Operating Grant

Multiple Sclerosis is a degenerative disease that affects over seventy thousand Canadians. Canada has some of the highest rates of MS in the world. It often strikes young people, making the disease burden high. MS is a chronic inflammatory disease in which the patient's own immune cells destroy neurons and myelin, the electrical insulation for axons. This causes neuronal dysfunction and conduction failure. MS has a broad range of motor and sensory dysfunction leading to weakness, paralysis and chronic pain. However, depression, fatigue, anxiety and cognitive function deficits are also common in MS but are often overlooked, poorly understood and poorly controlled. As they do not correlate well with severity of the disease the mechanism that underlies these comorbidities is unknown. In this research I will test the hypothesis that these behavioral problems arise from an effect of inflammatory mediators in the brain on the ability of neurons to communicate with each other at their specialized contacts called synapses. I will use a mouse model of MS, Experimental Autoimmune Encephalomyelitis, known as EAE, that displays co-morbid behaviors resembling those seen in MS. I will measure levels of inflammatory compounds in the brain and determine by using genetically modified mice or specialized drugs if these inflammatory compounds mediate the behaviors. Next, I will use electrical recording techniques to determine if synaptic function is changed and ask if the same mediators cause the electrical changes. Finally, I will ask if the underlying electrophysiological changes mediate the behaviors. These experiments will lay the groundwork for a better understanding and possible new avenues of therapy for behavioral comorbidity in MS.