Downregulation of LRP1 [correction of LPR1] at the blood-brain barrier in streptozotocin-induced diabetic mice.
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.
Hong
Hao
H
Department of Pharmacology, China Pharmaceutical University, Tong Jiaxiang, Nanjing 210009, PR China. haohongchina@hotmail.com
Liu
Li Ping
LP
Liao
Jian Ming
JM
Wang
Tong Sheng
TS
Ye
Feng Ying
FY
Wu
Jing
J
Wang
Ying Yu
YY
Wang
Ying
Y
Li
Yong Qi
YQ
Long
Yan
Y
Xia
Yuan Zheng
YZ
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*
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