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-κb pathway plays an important role in the pathophysiology of alzheimer's disease (ad),and blocking nf-κb pathway activation has been shown to attenuate cognitive impairment. diabetic metabolic disorder contributes to β-amyloid protein (aβ) generation. the goal of this study was to determine the effect of minocycline on aβ generation and the nf-κb 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-κb,cox-2,inos,il-1β and tnf-α after the stz injection were significantly increased in the hippocampus. significant increases in aβ,bace1,nf-κb,cox-2,inos,il-1β and tnf-α were found in diabetic rats. the levels of aβ,nf-κb,cox-2,inos,il-1β and tnf-α were significantly decreased after minocycline administration; however,minocycline had no effect on bace1 expression. in sum,diabetes contributes to the activation of the nf-κb pathway and upregulates bace1 and aβ. minocycline downregulates aβ in the hippocampus by inhibiting nf-κb pathway activation. copyright © 2011 by institute of pharmacology polish academy of sciences.