Memory loss caused by beta-amyloid protein is rescued by a beta3-adrenoceptor agonist

Marie Elizabeth Gibbs, Danuta Maria Maksel, Zoe Gibbs, Xu Hou, Roger James Summers, David Henry Small

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Abstract

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. [DOI:10.1016/j.neurobiolaging.2008.05.018]
Original languageEnglish
Pages (from-to)614 - 624
Number of pages10
JournalNeurobiology of Aging
Volume31
Publication statusPublished - 2010

Cite this

Gibbs, M. E., Maksel, D. M., Gibbs, Z., Hou, X., Summers, R. J., & Small, D. H. (2010). Memory loss caused by beta-amyloid protein is rescued by a beta3-adrenoceptor agonist. Neurobiology of Aging, 31, 614 - 624.