Following changes in brain structure and function with multimodal MRI in a year-long prospective study on the development of Type 2 diabetes.

Abstract

Aims: To follow disease progression in a rat model of Type 2 diabetes using multimodal MRI to assess changes in brain structure and function.

Material and methods: Female rats (n = 20) were fed a high fat/high fructose diet or lab chow starting at 90 days of age. Diet fed rats were given streptozotocin to compromise pancreatic beta cells, while chow fed controls received vehicle. At intervals of 3, 6, 9, and 12 months, rats were tested for changes in behavior and sensitivity to pain. Brain structure and function were assessed using voxel based morphometry, diffusion weighted imaging and functional connectivity.

Results: Diet fed rats presented with elevated plasma glucose levels as early as 3 months and a significant gain in weight by 6 months as compared to controls. There were no significant changes in cognitive or motor behavior over the yearlong study but there was a significant increase in sensitivity to peripheral pain in diet fed rats. There were region specific decreases in brain volume e.g., basal ganglia, thalamus and brainstem in diet fed rats. These same regions showed elevated measures of water diffusivity evidence of putative vasogenic edema. By 6 months, widespread hyperconnectivity was observed across multiple brain regions. By 12 months, only the cerebellum and hippocampus showed increased connectivity, while the hypothalamus showed decreased connectivity in diet fed rats.

Conclusions: Noninvasive multimodal MRI identified site specific changes in brain structure and function in a yearlong longitudinal study of Type 2 diabetes in rats. The identified diabetic-induced neuropathological sites may serve as biomarkers for evaluating the efficacy of novel therapeutics.