Block of purinergic P2X7 receptor is neuroprotective in an... : NeuroReport (original) (raw)
NEUROPHARMACOLOGY AND NEUROTOXICOLOGY
Block of purinergic P2X7 receptor is neuroprotective in an animal model of Alzheimer's disease
Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada
Correspondence to Dr James G. McLarnon, PhD, Department of Anesthesiology, Pharmacology and Therapeutics, 2176 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Tel: +604 822 5719; fax: +604 822 6012; e-mail: [email protected]
Received 30 July 2008; accepted 7 August 2008
Abstract
Pharmacological antagonism of the ionotropic purinergic P2X7R has been studied for effects on inflammatory reactivity and neuronal viability in amyloid-β1–42-injected rat hippocampus. Amyloid-β1–42-injected brains (7-day postinjection) demonstrated marked increases in P2X7R expression, gliosis, leakiness of blood–brain barrier and loss of hippocampal neurons. The P2X7R 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 P2X7R agonist, 2′,3′-(benzoyl-4-benzoyl)-ATP. The findings constitute the first report that pharmacological inhibition of P2X7R, possibly by acting to inhibit inflammatory reactivity, confers neuroprotection in an animal model of Alzheimer's disease brain.
© 2008 Lippincott Williams & Wilkins, Inc.