Mechanisms of central axon and myelin injury using advanced morphological and biochemical characterization
Date
2015-04-06
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Abstract
In the adult nervous system, white matter connecting brain, spinal, and peripheral regions is essential for neuron communication. In the white matter, the axon plays an essential role in transmitting nerve impulses, while myelin facilitates conduction through rapid propagation and optimal energy-consumption. White matter injury in the central nervous system, leading to the degeneration of axons and myelin, is commonly found in multiple sclerosis, anoxia, ischemic stroke, and traumatic brain and spinal cord injury. These lead to cognitive impairment, sensorimotor disability or death. During white matter injury, axonal spheroid formation (ASF) and demyelination are the pathological hallmarks of white matter degeneration. However, the mechanism by which this occurs is unknown. I hypothesize that focal spheroids are induced by activation of glutamate receptors and lead to local calcium overload in axons. To test this hypothesis, I established an ex vivo imaging model of central white matter dorsal column using two-photon microscopy to investigate this phenomenon. Ex vivo imaging of the white matter dorsal column with high-spatial resolution was achieved, which allowed the observation of morphology of axon and myelin before and during injury. The dynamic imaging of live myelinated axon response to injury suggests that axons and myelin are not as passive as previously thought. The data presented in this thesis support the notion of over-activation of glutamate receptors inducing ASF and a calcium rise leading to axonal transection. In addition, I established a novel method using solvatochromic dyes to investigate the biochemical property of myelin in which changes in the lipid composition served as a health indicator of myelin. The study of live myelin with solvatochromic dyes to stain myelin lipids could report different stages ranging from development, maturity, injury, and repair of myelin.
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Neuroscience
Citation
Teo, W. (2015). Mechanisms of central axon and myelin injury using advanced morphological and biochemical characterization (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26864