Increased amyloid β-peptide (1–40) level in brain of streptozotocin-induced diabetic rats

Abstract

The aims of the study were to investigate whether the level of amyloid β-peptide (Aβ) (1–40) was increased in brain of diabetic rats and whether the increase was associated with dysfunction of P-glycoprotein at the blood–brain barrier. A diabetes-like condition was induced by single administration of 65 mg/kg streptozotocin via i.p. injection. Aβ (1–40) levels in brain of the diabetic rats were measured using an enzyme linked immunosorbent assay (ELISA) kit. The in vivo brain-to-blood efflux and blood-to-brain influx transport of [ 125I]-labeled human amyloid-β-peptide (hAβ) (1–40) were measured using the brain efflux index and brain permeability coefficient-surface area product, respectively. [ 14C]inulin served as a reference compound. The results showed that Aβ (1–40) levels significantly increased in temporal cortex and hippocampus of the diabetic rats. The brain remaining percentage of [ 125I]hAβ (1–40) in diabetic rats significantly increased at 30 min after intracerebral microinjection, accompanied by decrease of the brain efflux index. Pretreatment of P-glycoprotein inhibitors verapamil or cyclosporin A significantly increased the brain remaining percentage of [ 125I]hAβ (1–40). The brain permeability coefficient-surface area product of [ 125I]hAβ (1–40) was increased in diabetic rats, accompanied by increased Aβ (1–40) levels in plasma. The present study demonstrated that a diabetic state could increase Aβ (1–40) levels in brain, which might be explained, at least in part, by the decline in brain-to-blood efflux of Aβ (1–40) due to deficient cerebral P-glycoprotein function in diabetic rats.