The Effect of Intrahippocampal Insulin Infusion on Spatial Cognitive Function and Markers of Neuroinflammation in Diet-induced Obesity

Obesity and high fat diet consumption contribute to the development of metabolic disorders, insulin resistance, neuroinflammation, and cognitive impairments. CNS administration of insulin into the brain can attenuate these cognitive impairments. The present study investigated whether hippocampal-dependent spatial memory impairments in a dietary induced mouse model of obesity could be improved by the direct administration of insulin into the hippocampus and whether this was associated with markers of hippocampal inflammation. C57Bl/6J mice consumed a low fat or high fat diet for 16 weeks and continuous intrahippocampal saline or insulin infusion for the final 4 weeks, during a period of behavioral testing, before gene expression analysis was performed. The high fat diet group demonstrated poorer spatial memory performance in the Morris water maze and Y-maze, supporting the hypothesis that high fat diet leads to hippocampal dependent cognitive impairment. Insulin infusion into the hippocampus reversed the deficit of high fat diet consumption on both of the tasks. Increased expression of inflammatory markers was detected in the hippocampus in the high fat diet group and expression of these markers was ameliorated in insulin infused mice. This demonstrates that CNS insulin can improve hippocampal-dependent memory and that hippocampal inflammation may be a factor in the development of cognitive deficits associated with diet-induced obesity. Furthermore, these data suggest that insulin may act to attenuate high fat diet induced cognitive deficits by reducing neuroinflammation.