Abstract TMP115: Diabetes-induced Neuronal Degeneration and Dysfunctional Neovascularization in the Hippocampus: Implications for Cognitive Impairment and Stroke

Abstract

Diabetes increases the risk of stroke and is associated with worsened cognitive outcome. We have shown that diabetes mediates immature and leaky new vessel formation in cortex and striatum and these changes are accompanied by cognitive deficits. However, the effect of diabetes on the vasculature in hippocampus, a major domain for memory and cognition, remained unknown. Hypothesis: Impaired cognitive function in diabetes is associated with neurovascular remodeling and activation of NLRP3 inflammasome in the hippocampus. Methods: Diabetes was induced through a high fat (45%) diet and 30mg/kg STZ injection in male Wistar rats (n=4). Vascular architecture was examined by space filling FITC. Immunohistochemistry was used to measure neuronal degeneration and NLRP3 expression. Cognitive function was assessed by novel object recognition test. Results: Vascular density and volume were increased the dentate gyrus (DG) and CA1, respectively, in diabetic rats. The DG had reduced numbers of neurons in diabetic rats, and the CA1, CA3 and DG all showed elevated cell death. Markers of the NLRP3, ASC and cryopyrin, showed elevated expression in the hippocampus. The recognition index was decreased in diabetic animals compared to control. Conclusions: These data suggest that the DG is sensitive to neurovascular remodeling in diabetes. Diabetes-induced NLRP3 activation may be involved in this remodeling and contribute to cognitive deficits in diabetes.