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Upregulation of RAGE at the blood‐brain barrier in streptozotocin‐induced diabetic mice
Author(s) -
Liu Li Ping,
Hong Hao,
Liao Jian Ming,
Wang Tong Sheng,
Wu Jing,
Chen Si Si,
Li Yong Qi,
Long Yan,
Xia Yuan Zheng
Publication year - 2009
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20644
Subject(s) - downregulation and upregulation , rage (emotion) , glycation , streptozotocin , blood–brain barrier , endocrinology , medicine , diabetes mellitus , western blot , chemistry , neuroscience , biology , central nervous system , biochemistry , gene
Deposition of amyloid‐β peptide (Aβ) 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 Aβ 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‐Aβ 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 Aβ showed significant RAGE‐dependent transport of Aβ 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 Aβ deposition in the diabetes. Synapse 63:636–642, 2009. © 2009 Wiley‐Liss, Inc.