Upregulation of RAGE at the blood-brain barrier in streptozotocin-induced diabetic mice.
Deposition of amyloid-beta peptide (Abeta) in the brain of diabetes is poorly understood. The receptor for advanced glycation end products (RAGE) at the blood-brain barrier (BBB) is critical for regulation of Abeta homeostasis in the brain. In this studies, we used streptozotocin-induced diabetic mice to observe the expression of RAGE at the BBB by Western blot and immunocytochemical analysis, and the in vivo blood-to-brain influx transport of (125)I-Abeta(1-) (40) using the permeability surface area product (PS) and brain capillary uptake. In the diabetic mice with hyperglycemia (>16.0 mmol/L) at 6 weeks, RAGE expression at the BBB was significantly upregulated, no significant changes of RAGE levels were found at 1 and 3 weeks after diabetes induction. The data of PS and brain capillary uptake for Abeta showed significant RAGE-dependent transport of Abeta across the BBB and substantial RAGE-dependent brain capillary uptake at 6 weeks after diabetes induction. We conclude that the upregulation of RAGE at the BBB contributes to cerebral Abeta deposition in the diabetes.
Department of Pharmacy, First Hospital Affiliated to Anhui Medical University, Hefei, China.
Li Ping
LP
Liu
Hao
H
Hong
Jian Ming
JM
Liao
Tong Sheng
TS
Wang
Jing
J
Wu
Si Si
SS
Chen
Yong Qi
YQ
Li
Yan
Y
Long
Yuan Zheng
YZ
Xia
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D006442:Glycated Hemoglobin / Q000031:analogs & derivatives / Q000378:metabolism; D007554:Isotopes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007554:Isotopes; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42); C025617:glucosylated hemoglobin A