title: Downregulation of LRP1 [correction of LPR1] at the blood-brain barrier in streptozotocin-induced diabetic mice.
abstract: Deposition of amyloid-beta peptide (Abeta) 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 Abeta 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-Abeta1-40 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 Abeta showed significant decrease in LRP1-dependent transport of Abeta across the BBB at 6 weeks after diabetes induction, while no significant changes of LRP1-dependent transport of Abeta 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 Abeta deposition in diabetes mellitus.
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Tong Jiaxiang, Nanjing 210009, PR China. haohongchina@hotmail.com
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Liu
authors.forename: Jian Ming
authors.initials: JM
authors.lastname: Liao
authors.forename: Tong Sheng
authors.initials: TS
authors.lastname: Wang
authors.forename: Feng Ying
authors.initials: FY
authors.lastname: Ye
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Ying Yu
authors.initials: YY
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong Qi
authors.initials: YQ
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Long
authors.forename: Yuan Zheng
authors.initials: YZ
authors.lastname: Xia
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism; D011973:Receptors, LDL / Q000096:biosynthesis*; D013311:Streptozocin; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D016229:Amyloid beta-Peptides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D010446:Peptide Fragments; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; C078592:amyloid beta-protein (1-40); D013311:Streptozocin