科研之友
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摘要
Deposition of amyloid-beta peptide (A beta) in the diabetic brain is poorly understood. Low-density lipoprotein receptor related protein 1(LRP1) at the blood-brain barrier (BBB) is critical for regulation of A beta homeostasis in the brain. in this study, we used streptozotocin-induced diabetic mice to observe the expression of LRP1 at the BBB by Western blot and immunocytochemical analysis, and to study in vivo brain-to-blood efflux transport of (125)I-A beta 1-40 using brain clearance studies. In the diabetic mice with hyperglycemia (>16.0 mmol/l) at 6 weeks, LRP1 expression at the BBB was significantly downregulated; no significant changes of LRP1 levels were found at 1 and 3 weeks after diabetes induction. The data of brain clearance studies for A beta showed significant decrease in LRP1-dependent transport of A beta across the BBB at 6 weeks after diabetes induction, while no significant changes of LRP1-dependent transport of A beta across the BBB at 1 or 3 weeks after diabetes induction were apparent. We conclude that the down-regulation of LRPI at the BBB contributes to cerebral A beta deposition in diabetes mellitus.
