Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.777363
Title: Cellular organisation of peripheral nerve and the neuromuscular junction
Author: Court, Felipe A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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Abstract:
The organisation of cells in the peripheral nervous system is crucial for its proper function. Action potential generation, conduction and synaptic transmission to the muscle fibres are dependent not only on cells directly implicated in these functions (i.e. neurons and muscle fibers) but also on accessory cells with important modulatory roles. These cells are also essential for adaptive responses by the peripheral nervous system during development, injury and pathological conditions. Schwann cells represent one of the principal cellular components regulating nerve function. In peripheral nerves, myelin-forming Schwann cells specify distinct domains in the axon, allowing fast and efficient propagation of the action potential. At the neuromuscular junction, terminal Schwann cells are necessary for stability of motor nerve terminals and motor endplates and they are involved in plastic responses of the neuromuscular system to injury and in disease. This thesis is a study of how the cellular organisation of the peripheral nerve and neuromuscular junction determines their morphological and electrophysiological characteristics as well as their functional role in plastic responses following destabilizing stimuli. The mechanism by which Schwann cells regulate the length of the myelinated segment over the axon is addressed and this parameter, i.e. the internodal length, is shown experimentally for the first time as a key determinant of nerve conduction velocity (Court et al., 2004). At the neuromuscular junction, immunostaining with a panel of antibodies revealed a novel cell type, distinct from Schwann cells and possibly related to fibroblasts. These cells lie outside the synaptic basal lamina, but in adults they are highly restricted to the neuromuscular junction. Studies of the development of the novel cells, and their reaction to nerve injury and paralysis, suggest they play a crucial role in the maintenance and disposition of motor nerve terminals and terminal Schwann cells. Finally, studies of periaxin null mutant mice, which show a demyelinating neuropathy, yielded new insights into the relationships between axons and Schwann cells at the neuromuscular junction. Defects observed in morphology and electrophysiology of junctions in these mice may contribute to their behavioural phenotype (i.e. trembling, weakness), suggesting that disruption of nerve terminal-Schwann cell relationships may also contribute to disability in demyelinating diseases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.777363  DOI: Not available
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