This thesis describes the study of the neurochemistry of Huntington's disease using a large series of post mortem brain tissue taken from patients with Huntington's disease and from matching controls with no previous history of neuropsychiatric disorder. There were two main aims: firstly, to identify and characterise any altered parameters of neurotransmitter systems, especially in relation to the symptomatology of the disease; secondly, to understand the role of neurotoxins in the aetiology of the disease, particularly endogenous compounds that may have derived from aberrant metabolism. Concentrations of the amino acid transmitters, GABA and glutamate, were generally significantly decreased throughout the brain in Huntington's disease, including cortical and limbic regions. Cortical deficits were not associated with the dementia of the disease, whereas caudate levels of GABA and glutamate showed a relationship with the dementia. In patients with severe chorea, the medial pallidum was found to have a relatively smaller GABA deficit than mildly choreic patients. Another novel finding was that 5HT and 5HIAA concentrations were significantly increased in most regions of the brain in Huntington's disease, perhaps reflecting abnormal tryptophan metabolism. Such changes in the cortex provide evidence for a cortical involvement in the disease. Dopamine metabolism appeared to be reduced in Huntington's disease, reflected by the significantly decreased concentrations of its major metabolite, homovanillic acid, in most regions except for the cortex (where it was increased). Neuroactive compounds of the kynurenine pathway of tryptophan metabolism were measured in Huntington's disease. Quinolinic acid concentrations were not significantly altered, however 3- hydroxykynurenine concentrations were significantly increased in the striatum and cortex. This provides the first evidence for increased concentrations of an endogenous neurotoxic compound in the brain in Huntington's disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:317625 |
| Date | January 1992 |
| Creators | Pearson, Sally Jane |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/28467/ |
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