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Title: A pathophysiological study of the hippocampus in a presenilin 1 M146V rat model of Alzheimer's disease
Author: Pybus, Ruth
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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This thesis investigates the hippocampal electrophysiology and pathology of a rat model of the M146V mutation to the presenilin 1 gene. This is the first rat model of presenilin 1 AD. This mutation causes dominant inheritance of AD in a Finnish family. Since affected subjects show early disease onset and rapid deterioration, it was hoped that the PS1M146V transgene would promote generation of a phenotype within the life-span of the rat. In this study, extracellular field potential recordings of medial perforant pathway/dentate gyrus and CA3/CA1 synaptic properties and plasticity have been made in the PSIM146V transgenic rats and their non-transgenic littermates at 6 and 18 months old. At 6 months, no changes were seen in the expression of long-term potentiation, post-tetanic potentiation or paired pulse plasticity in either pathway. Synaptic plasticity recorded in the dentate gyrus in 18 months animals was also unchanged. However, long-term potentiation was significantly increased in the CA3/CA1 pathway in 18 month old transgenic animals, which showed a striking difference in its pattern of development. Paired pulse facilitation and post-tetanic potentiaion were unchanged. This age-dependent and pathway-specific change is consistent with the progression of AD in human subjects, and results published on presenilin 1 mouse models. Intracellular sharp electrode recordings were made from CA1 pyramidal neurones from the 18 month old animals to investigate the source of the changes in long-term potentiaion. No changes were observed in the passive membrane properties, action potential properties, the duration or amplitude of slow, medium and fast afterhyperpolarization and action potential adaptation. However, the half width of the EPSP was significantly increased, which may be attributable to slower repolarization.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available