Memory loss caused by beta-amyloid protein is rescued by a beta(3)-adrenoceptor agonist.
Accumulation of the neurotoxic beta-amyloid protein (Abeta) in the brain is a key step in the pathogenesis of Alzheimer's disease (AD). Although transgenic mouse models of AD have been developed, there is a clear need for a validated animal model of Abeta-induced amnesia which can be used for toxicity testing and drug development. Intracranial injections of Abeta(1-42) impaired memory in a single trial discriminative avoidance learning task in chicks. Memory inhibition was closely associated with the state of aggregation of the Abeta peptide, and a scrambled-sequence of Abeta(1-42) peptide failed to impair memory. Abeta had little effect on labile (short-term and intermediate) memory, but blocked consolidation of memory into long-term storage mimicking the type of anterograde amnesia that occurs in early AD. Since noradrenaline exerts a modulatory influence on labile memory in the chick, we examined the effects of two beta-adrenoceptor (AR) agonists on Abeta-induced amnesia. A beta(3)-AR agonist (CL316243), but not a beta(2)-AR agonist, rescued Abeta-induced memory loss, suggesting the need for further studies on the role of beta(3)-ARs in AD.
Gibbs
Marie E
ME
Department of Anatomy and Developmental Biology, Monash University, Clayton Campus, Wellington Road, Clayton, Victoria 3800, Australia. marie.gibbs@med.monash.edu.au
Maksel
Danuta
D
Gibbs
Zoe
Z
Hou
Xu
X
Summers
Roger J
RJ
Small
David H
DH
D000322:Adrenergic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058667:Adrenergic beta-3 Receptor Agonists; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020324:Amnesia, Anterograde / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002645:Chickens; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D016896:Treatment Outcome
D000322:Adrenergic Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D016229:Amyloid beta-Peptides; D004149:Dioxoles; D010446:Peptide Fragments; D022702:Receptors, Adrenergic, beta-3; C075222:amyloid beta-protein (1-42); C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate