Volume Changes in the Striosomes in Transgenic Sheep Models with Huntington’s disease

Abstract

Huntington’s disease is a familial neurodegenerative disease, caused by an expanded polyglutamine stretch located on exon 1 of chromosome 4. The downstream consequences of this mutation are neurotoxicity and loss of tissue mass, predominantly in the regions of the cortex and striatum. Within the striatum there are Medium Spiny Neurons which are particularly susceptible to degeneration in comparison with the other neuronal cell types. The underlying reason for the neurotoxicity has been attributed to: glutamate excitotoxicity, disruption of signalling pathways, oxidative stress, transcriptional deregulation and mutant huntingtin fragment aggregates. However, there is still debate over some of the disease mechanisms. The loss of neurons in regions of the brain is attributed to the region specific reduction in tissue mass; this can be observed in post-mortem brain cases. In this thesis, the volume of the striosomes within the caudate nucleus will be measured using the Cavalieri principle. Comparisons will be made between the control and transgenic 5 year old sheep cases, to determine if there is a significant reduction between the two groups. The outcomes of this study provide further insight into the validity of whether or not the transgenic Huntington’s disease sheep model is a good model of human Hungtington’s Disease.