Downregulation of LPR1 at the blood–brain barrier in streptozotocin-induced diabetic mice

• Published in: Neuropharmacology Vol. 56; no. 6; pp. 1054 - 1059
• Main Authors: Hong, Hao, Liu, Li Ping, Liao, Jian Ming, Wang, Tong Sheng, Ye, Feng Ying, Wu, Jing, Wang, Ying Yu, Wang, Ying, Li, Yong Qi, Long, Yan, Xia, Yuan Zheng
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2009
• Subjects: Amyloid-β peptide; Blood–brain barrier; Diabetes mellitus; Low-density lipoprotein receptor related protein; Aβ; AD; BBB; LRP1; Diabetes mellitus; Low-density lipoprotein receptor related protein; STZ; DM; CNS; Amyloid-β peptide; Blood–brain barrier
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2009.03.001

Deposition of amyloid-β peptide (Aβ) 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 Aβ 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 125I-Aβ1–40 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 Aβ showed significant decrease in LRP1-dependent transport of Aβ across the BBB at 6 weeks after diabetes induction, while no significant changes of LRP1-dependent transport of Aβ across the BBB at 1 or 3 weeks after diabetes induction were apparent. We conclude that the downregulation of LRP1 at the BBB contributes to cerebral Aβ deposition in diabetes mellitus.