The project described in this thesis began with a broad analysis of the changes to amino acid and biogenic amine concentrations in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of Multiple Sclerosis (MS). That study identified deficits in specific neurotransmitters during EAE that I targeted pharmacologically using the antidepressant drug phenelzine. Phenelzine administration substantially influenced the concentrations of amino acids and biogenic amines in EAE mice in a manner likely to be therapeutic. In the final experiment, I treated EAE mice chronically with phenelzine; This treatment was associated with significant improvements in motor abilities compared to vehicle treated animals. In an open field, improvements were also observed in behavioural indices of depression, physical sickness and anxiety. The results of this thesis may offer new insights into the pathogenesis of EAE and MS and indicate the disease-modifying potential of phenelzine treatment in MS.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1950 |
| Date | 11 1900 |
| Creators | Musgrave, Travis |
| Contributors | Dr. Bradley Kerr (Anesthesiology and Pain Medicine), Dr. Peter Smith (Pharmacology), Dr. Karim Fouad (Rehabilitation Medicine), Dr. Glen Baker (Psychiatry) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 4306969 bytes, application/pdf |
| Relation | Musgrave, T., Tenorio, G., Rauw, G., Baker, G.B., and Kerr, B.J. (2011). Tissue concentration changes of amino acids and biogenic amines in the central nervous system of mice with experimental autoimmune encephalomyelitis (EAE). Neurochemistry International (in press) |
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