Increases in β-amyloid protein in the hippocampus caused by diabetic metabolic disorder are blocked by minocycline through inhibition of NF-κB pathway activation

Activation of the NF-kappa B pathway plays an important role in the pathophysiology of Alzheimer's disease (AD), and blocking NF-kappa B pathway activation has been shown to attenuate cognitive impairment. Diabetic metabolic disorder contributes to beta-amyloid protein (A beta) generation. The goal of this study was to determine the effect of minocycline on A beta generation and the NF-kappa B pathway in the hippocampus of diabetic rats and to elucidate the neuroprotective mechanisms of minocycline for the treatment of diabetic metabolic disorder. The diabetic rat model was established using a high-fat diet and an intraperitoneal injection of streptozocin (STZ). Behavioral tests showed that the capacity of learning and memory was significantly lower in diabetic rats. The levels of NF-kappa B, COX-2, iNOS, IL-1 beta and TNF-alpha after the STZ injection were significantly increased in the hippocampus. Significant increases in A beta, BACE1, NF-kappa B, COX-2, iNOS, IL-1 beta and TNF-alpha were found in diabetic rats. The levels of A beta, NF-kappa B, COX-2, iNOS, IL-1 beta and TNF-alpha were significantly decreased after minocycline administration; however, minocycline had no effect on BACE1 expression. In sum, diabetes contributes to the activation of the NF-kappa B pathway and upregulates BACE I and A beta. Minocycline downregulates A beta in the hippocampus by inhibiting NF-kappa B pathway activation.