Pharmacological Inhibition of Galectin-3 Ameliorates Diabetes-Associated Cognitive Impairment, Oxidative Stress and Neuroinflammation in vivo and in vitro.

Background In diabetes, cognitive impairment is linked with oxidative stress and neuroinflammation. As the only chimeric member of the galectin family, galectin-3 (Gal3) induces neuroinflammation and cognitive impairment in models of Alzheimer's disease (AD); however, its role in diabetes-associated cognitive impairment is not established. Methodology Here, we investigated the effects of Gal3 inhibition on cognitive impairment and the possible underlying molecular events in diabetes. We investigated the effects of the Gal3 inhibitor modified citrus pectin (MCP; 100 mg/kg/day oral for 6 weeks) in vivo in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Additionally, the effects of MCP on high glucose (HG)-stimulated BV-2 microglial cells were investigated in vitro. Results We found that MCP attenuated memory impairment in diabetic rats in the Morris water maze test and reduced insulin resistance, oxidative stress, and neuroinflammation. In HG-stimulated BV-2 microglial cells, MCP increased cell viability and decreased oxidative stress and the production of proinflammatory cytokines. Conclusion The results of this study indicate that the inhibition of Gal3 by MCP ameliorates diabetes-associated cognitive impairment, oxidative stress, and neuroinflammation, suggesting that Gal3 could be a potential new target for therapeutic intervention to prevent cognitive impairment in diabetes.