Research over the last two decades has revealed that the process of neurogenesis continues in some brain regions throughout adulthood in mammals. The dentate gyrus of the hippocampal formation displays adult neurogenesis and is known to be critical for some forms of learning and memory. Adult neurogenesis has been proposed to play an important role in hippocampal function.
Seizures have been found to increase the rate of adult neurogenesis as well as alter the development of newborn neurons. Seizure-induced changes in neurogenesis have been proposed to underlie some of the cognitive impairments seen in epileptic patients. This thesis examines changes in neurogenesis in the dentate gyrus in the kindling model of temporal lobe epilepsy in rats, and explores the potential impact of these changes on hippocampal function.
Progenitor cell proliferation and net neurogenesis were found to be increased in kindled rats, but increased proliferation was not sustained and returned to baseline by 8 days. This increase was greater in dorsal than ventral dentate gyrus but did not differ among the blades of the granule cell layer.
Kindled seizures were found to enhance the survival of newborn neurons when presented during the second week of their development. These survived for at least 1 month after kindling (6 weeks after their birth).
Electrical stimulation at current intensities below afterdischarge threshold failed to alter progenitor cell proliferation, while currents above threshold greatly increased it. There was no relationship found between stimulation current intensity and the rate of cell proliferation.
Bilateral kindling of the perforant path failed to alter learning or long-term memory in a water maze test in spite of a large increase in neurogenesis in the dentate gyrus. Unkindled rats with more new neurons showed better learning performance, but had poorer long-term memory in the task. Kindled rats showed a disruption of these relationships.
This thesis found that neurogenesis was greatly increased in the kindling epilepsy model, but that performance in a commonly used learning/memory task was unaltered. The impact of kindled seizures on water maze performance is questioned as well as the relevance of enhanced neurogenesis to cognitive impairments in epilepsy.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/43722 |
| Date | 14 January 2014 |
| Creators | Scott, Brian Wayne |
| Contributors | Burnham, W. McIntyre |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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