Upregulation of RAGE at the Blood-Brain Barrier in Streptozotocin-Induced Diabetic Mice

被引:41
作者
Liu, Li Ping [3 ]
Hong, Hao [1 ]
Liao, Jian Ming [2 ]
Wang, Tong Sheng [3 ]
Wu, Jing [1 ]
Chen, Si Si [1 ]
Li, Yong Qi [1 ]
Long, Yan [1 ]
Xia, Yuan Zheng [1 ]
机构
[1] China Pharmaceut Univ, Dept Pharmacol, Nanjing 210009, Peoples R China
[2] China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Peoples R China
[3] Anhui Med Univ, Affiliated Hosp 1, Dept Pharm, Hefei 230036, Peoples R China
关键词
receptor for advanced glycation end products (RAGE); amyloid-beta peptide; blood-brain barrier (BBB); diabetes; Alzheimer's disease; AMYLOID-BETA; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; PEPTIDE; RECEPTOR; RATS; CLEARANCE; TRANSPORT; PRODUCTS; MELLITUS;
D O I
10.1002/syn.20644
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Deposition of amyloid-beta peptide (A beta) 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 A beta 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 I-125-A beta(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 A beta showed significant RAGE-dependent transport of A beta 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 A beta deposition in the diabetes. Synapse 63:636-642,2009. (c) 2009 Wiley-Liss, Inc.
引用
收藏
页码:636 / 642
页数:7
相关论文
共 32 条
  • [1] Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function
    Arvanitakis, Z
    Wilson, RS
    Bienias, JL
    Evans, DA
    Bennett, DA
    [J]. ARCHIVES OF NEUROLOGY, 2004, 61 (05) : 661 - 666
  • [2] Begley DJ, 2003, PROG DRUG RES, V61, P39
  • [3] AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept
    Bierhaus, A
    Hofmann, MA
    Ziegler, R
    Nawroth, PP
    [J]. CARDIOVASCULAR RESEARCH, 1998, 37 (03) : 586 - 600
  • [4] The impact of diabetes on cognition: What can be learned from rodent models?
    Biessels, GJ
    Gispen, WH
    [J]. NEUROBIOLOGY OF AGING, 2005, 26 : S36 - S41
  • [5] Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment
    Biessels, GJ
    Kamal, A
    Urban, IJA
    Spruijt, BM
    Erkelens, DW
    Gispen, WH
    [J]. BRAIN RESEARCH, 1998, 800 (01) : 125 - 135
  • [6] GLYCATION PRODUCTS AND THE PATHOGENESIS OF DIABETIC COMPLICATIONS
    BROWNLEE, M
    [J]. DIABETES CARE, 1992, 15 (12) : 1835 - 1843
  • [7] RAGE (Yin) versus LRP (Yang) balance regulates Alzheimer amyloid β-peptide clearance through transport across the blood-brain barrier
    Deane, R
    Wu, ZH
    Zlokovic, BV
    [J]. STROKE, 2004, 35 (11) : 2628 - 2631
  • [8] LRP/amyloid β-peptide interaction mediates differential brain efflux of Aβ isoforms
    Deane, R
    Wu, ZH
    Sagare, A
    Davis, J
    Yan, SD
    Hamm, K
    Xu, F
    Parisi, M
    LaRue, B
    Hu, HW
    Spijkers, P
    Guo, H
    Song, XM
    Lenting, PJ
    Van Nostrand, WE
    Zlokovic, BV
    [J]. NEURON, 2004, 43 (03) : 333 - 344
  • [9] RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain
    Deane, R
    Yan, SD
    Submamaryan, RK
    LaRue, B
    Jovanovic, S
    Hogg, E
    Welch, D
    Manness, L
    Lin, C
    Yu, J
    Zhu, H
    Ghiso, J
    Frangione, B
    Stern, A
    Schmidt, AM
    Armstrong, DL
    Arnold, B
    Liliensiek, B
    Nawroth, P
    Hofman, F
    Kindy, M
    Stern, D
    Zlokovic, B
    [J]. NATURE MEDICINE, 2003, 9 (07) : 907 - 913
  • [10] Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease
    Deane, Rashid
    Zlokovic, Berislav V.
    [J]. CURRENT ALZHEIMER RESEARCH, 2007, 4 (02) : 191 - 197