Master of Science (MSc)
Faculty of Science
Type 2 diabetes mellitus is a disease that adversely affects cognitive function in areas extending to memory and executive functioning. The Goto-Kakizaki (GK) rat provides a model of type 2 diabetes that can illustrate the mechanisms by which this disease works. The present study compared hyperglycaemic GK rats and age-matched Wistar rats in the Morris water maze to assess spatial memory, and in a perceptual attentional set-shifting task to assess putative prefrontal-dependent executive functioning. Results showed there was no difference in path length during training trials, however, GK and Wistar rats differed in the path length travelled in the target quadrant during the probe trial. Although search strategies became more precise for both strains over the spatial training days, GK rat search strategies were less precise than Wistar rats. A urinary glucose test performed on the first and last days of water maze testing revealed that urine glucose significantly decreased after the water maze for GK rats. Golgi-Cox staining was used to examine dendritic complexity and spine densities in the suprapyramidal layer of the dentate gyrus. There was significantly less dendritic arbour and branching complexity in the GK rat dentate gyrus, particularly in the middle molecular layer. Spine densities were significantly decreased for GK rats in each molecular layer in the suprapyramidal blade. Results suggest that spatial memory retrieval deficits may be linked to diabetes, a mechanism thought to be associated with the dentate gyrus.
In the attentional set-shifting task, Day 1 of the task involved training rats to dig for food rewards and discriminate between different odours, digging mediums, and textures. Day 2 of the task consisted of a series of 7 shifts including discriminations, an intradimensional shift, an extradimensional shift, and 3 reversals. GK rats required significantly more trials to reach criterion in the discriminations, but not the other shifts. Duration of the discrimination and reversal 1 trials were also significantly greater for the GK rats. Urinary glucose tests validated hyperglycemia both before and after the task. Golgi-Cox staining was used to examine pyramidal neuron spine densities in the prelimbic cortex. Spine densities were significantly decreased for GK rats in layers II/III in the basilar and apical dendrites. Results suggest that GK rats have morphological changes in the prefrontal cortex despite having preserved executive function. The cognitive deficits observed in GK rats appear to be related to altered perception rather than executive functioning.
Keywords: Goto-Kakizaki rat; type 2 diabetes; dentate gyrus; prelimbic cortex
Dietze, Lorielle, "SPATIAL MEMORY AND EXECUTIVE FUNCTIONING IN THE GOTO-KAKIZAKI RAT MODEL OF DIABETES" (2020). Theses and Dissertations (Comprehensive). 2240.