Development of a novel in vitro model system to characterize the role of activity in motor neurons during development and disease
Neural activity modulates motor axon guidance and synaptic function during development. Differences in neural activity also contribute to the demise of specific motor neuron subtypes in amyotrophic lateral sclerosis (ALS). Studying the cellular mechanisms underlying these activity-dependent processes is complicated due to the inability to precisely activate motor neurons separate from other cell types. Here, we resolve this issue by generating embryonic stem cell-derived motor neurons (ESCMNs) expressing channelrhodopsin-2 (ChR2). ChR2 ESCMNs depolarize and fire single action potentials when pulsed by light. Chronic light activation of ChR2 ESCMNs (0.025 Hz for 2 days) increases neurite outgrowth, mediated by enhanced expression of polysialylated NCAM (PSA-NCAM). ChR2 ESCMNs expressing SOD1G93A, a mutation causing ALS, form neuromuscular junctions in vitro, but unlike wild-type counterparts, fail to maintain functional connections over time. Together, this thesis introduces a novel model system to study cellular mechanisms underlying activity-dependent modulation of motor neuron development and disease.
- Motor neuron disease
- Amyotrophic Lateral Sclerosis
- Neural Activity
- Neural Cell Adhesion Molecule
- Polysialic Acid
- Neurite Outgrowth
- Activity dependent
- Light Activation
- Neuromuscular junction
- Embryonic Stem Cells
- Embryonic Stem Cell derived motor neurons
Showing items related by title, author, creator and subject.
An Exploratory Study to Examine the Relationship between Academic Achievement and Physical Activity of Girls in Grades Three to Seven Participating in a Community-based Physical Activity Program Whittle, Krista (2011-12-15)The purpose of this mixed methods study was to better understand the relationship between physical activity and academic achievement of girls in grades three to seven participating in a community-based physical activity ...
Exploring the Relationships Between Healthy Active Living Marketing and Family Eating and Physical Activity Perceptions and Behaviours Orava, Taryn, A. (2010-08-17)Canada’s obesogenic environment is host to the advironment, which bombards children with advertisements for soft drinks, fast foods, confectionary, cereals and savory snacks (‘the Big 5’). Television is the primary media ...
Synthesis and three-dimensional quantitative structure-activity relationship studies of uracil-based molecules as potential antiepileptic active prodrugs. Buhendwa, Musole Guillain. (Dalhousie University, 2006)