Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/29957
Title: The physiology and pathophysiology of central axons
Authors: Alix, James John Philip
Award date: 2006
Presented at: University of Leicester
Abstract: This thesis investigates the physiology underlying central axon development and the pathophysiology of ischaemic injury to both immature and mature central axons, using the murine optic nerve model. A central theme to the work is that voltage gated Ca2+ channels (VGCCs) are involved in both axon development and injury. First, electrophysiological and immunohistochemical techniques were used to describe the expression of L-type and P/Q-type VGCCs at early developmental time points. Following this, two strains of mice, leaner and ducky2J, in which P/Q-type VGCC function is compromised, were used to ascertain what the function of this channel subtype might be. Malformation of nodes of Ranvier, disrupted targeting of nodal proteins and alterations in axon morphology, some subtle, some significant, are reported. These findings imply that P/Q-type VGCCs play an important role in regulating central axon development. Subsequent to this I investigated the hypothesis that VGCCs expressed during development contribute to ischaemic injury of developing axons. Simulation of ischaemia, by withdrawal of oxygen and glucose (OGD), resulted in irreversible injury and a minor role in the injury pathway could be ascribed to VGCCs; the major pathways are reported as being Ca2+ influx via ionotropic glutamate receptors. The final data offered in this thesis regard the ischaemic injury of mature, myelinated axons. N-methyl-D-aspartate (NMDA) receptor antagonism conferred a small but significant degree of protection against irreversible injury, indicating a change in the modality of OGD-mediated injury over time..
Links: http://hdl.handle.net/2381/29957
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, Dept. of Cell Physiology and Pharmacology
Leicester Theses

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