Abstract
Pharmacological antagonism of the ionotropic purinergic P2X7R has been studied for effects on inflammatory reactivity and neuronal viability in amyloid-beta1-42-injected rat hippocampus. Amyloid-beta1-42-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphate / administration & dosage
-
Adenosine Triphosphate / analogs & derivatives
-
Adenosine Triphosphate / pharmacology
-
Alzheimer Disease / chemically induced
-
Alzheimer Disease / metabolism*
-
Alzheimer Disease / pathology
-
Amyloid beta-Peptides / administration & dosage
-
Amyloid beta-Peptides / toxicity
-
Animals
-
Blood-Brain Barrier / drug effects
-
Blood-Brain Barrier / metabolism
-
Blood-Brain Barrier / pathology
-
Disease Models, Animal
-
Gliosis / metabolism
-
Gliosis / pathology
-
Hippocampus / drug effects
-
Hippocampus / metabolism
-
Hippocampus / pathology
-
Immunohistochemistry
-
Male
-
Neurons / drug effects
-
Neurons / metabolism*
-
Neurons / pathology
-
Neuroprotective Agents / agonists
-
Neuroprotective Agents / antagonists & inhibitors
-
Neuroprotective Agents / metabolism*
-
Peptide Fragments / administration & dosage
-
Peptide Fragments / toxicity
-
Platelet Aggregation Inhibitors / administration & dosage
-
Platelet Aggregation Inhibitors / pharmacology
-
Purinergic P2 Receptor Agonists
-
Purinergic P2 Receptor Antagonists
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, Purinergic P2 / metabolism*
Substances
-
Amyloid beta-Peptides
-
Neuroprotective Agents
-
Peptide Fragments
-
Platelet Aggregation Inhibitors
-
Purinergic P2 Receptor Agonists
-
Purinergic P2 Receptor Antagonists
-
Receptors, Purinergic P2
-
amyloid beta-protein (1-42)
-
3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
-
Adenosine Triphosphate