Block of purinergic P2X7 receptor is neuroprotective in an animal model of Alzheimer's disease

被引：118
作者：
Ryu, Jae K. [1 ]
McLarnon, James G. [1 ]
机构：
[1] Univ British Columbia, Dept Anesthesiol Pharmacol & Therapeut, Vancouver, BC V6T 1Z3, Canada
来源：
NEUROREPORT | 2008年 / 19卷 / 17期
关键词：
Alzheimer's disease animal model; amyloid-beta-peptide; blood-brain barrier; inflammatory reactivity; microglia; neuroprotection; purinergic P2X(7) receptor; P2X(7) receptor antagonist brilliant blue G;
D O I：
10.1097/WNR.0b013e3283179333
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Pharmacological antagonism of the ionotropic purinergic P2X(7)R has been studied for effects on inflammatory reactivity and neuronal viability in amyloid-beta(1-42)-injected rat hippocampus. Amyloid-beta(1-42)-injected brains (7-day postinjection) demonstrated marked increases in P2X(7)R expression, gliosis, leakiness of blood-brain barrier and loss of hippocampal neurons. The P2X(7)R antagonist, brilliant blue G reduced levels of purinergic receptor expression, attenuated gliosis, diminished leakiness of blood-brain barrier and was neuroprotective in peptide-injected brain. Brilliant blue G also demonstrated neuroprotection and antagonism against inflammatory responses induced by the P2X(7)R agonist, 2',3'-(benzoyl-4-benzoyl)-ATP. The findings constitute the first report that pharmacological inhibition of P2X(7)R, possibly by acting to inhibit inflammatory reactivity, confers neuroprotection in an animal model of Alzheimer's disease brain. NeuroReport 19:1715-1719 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
引用
收藏
页码：1715 / 1719
页数：5
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