Exercise rescues cognitive impairment through the fibrinogen pathway in diabetes

AbstractBackground:Fibrinogen is proved to play a vital role in the activation of neuroinflammation. Exercise rescues the cognitive deficits due to diabetes. However, the molecular protective mechanism of exercise mediated by fibrinogen cascade following BBB leakage still remains elusive in diabetes.Methods:This research focused on assessing the influence of fibrinogen on neuroinflammation and blood-brain barrier(BBB) and the role of exercise in improving cognitive function in diabetic rats by using stereotaxic FGG-AAV(fibrinogen gamma chain with adeno-associated viral vector )injection procedures.Results:Exercise improved learning and memory function by inhibiting fibrinogen level in diabetic rats. Exercise intervention decreased the production and activation of microglia and astroglia of diabetic rats. Increased FGG expression in diabetic rats significantly inhibited the protective effects of exercise on hippocampal EB leakage, BBB-related protein ZO-1 and Claudin-5 expression, and MMP-9 protein expression level. The expression level of inflammatory factors IL-1β and TNFαwere inhibited in exercise group, while overexpressing FGG level would compromise the protective effects of exercise.Conclusion:Exercise can improve cognitive impairment in diabetic rats by down-regulating the expression of fibrinogen, inhibiting the neuroinflammation process, and reducing blood-brain barrier damage.